全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
Cancers  2014 

The Complex Function of Hsp70 in Metastatic Cancer

DOI: 10.3390/cancers6010042

Keywords: Hsp70, metastasis, invasion, trafficking, lysosome

Full-Text   Cite this paper   Add to My Lib

Abstract:

Elevated expression of the inducible heat shock protein 70 (Hsp70) is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular Hsp70 has been recognized as a “chaperokine”, activating antitumor immunity. In this review we discuss localization dependent functions of Hsp70 in the context of invasive cancer. Understanding the molecular principles of metastasis formation steps, as well as interactions of the tumor cells with the microenvironment and the immune system is essential for fighting metastatic cancer. Although Hsp70 has been implicated in different steps of the metastatic process, the exact mechanisms of its action remain to be explored. Known and potential functions of Hsp70 in controlling or modulating of invasion and metastasis are discussed.

References

[1]  Kampinga, H.H.; Hageman, J.; Vos, M.J.; Kubota, H.; Tanguay, R.M.; Bruford, E.A.; Cheetham, M.E.; Chen, B.; Hightower, L.E. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 2009, 14, 105–111, doi:10.1007/s12192-008-0068-7.
[2]  Morimoto, R.I. Cells in stress: Transcriptional activation of heat shock genes. Science 1993, 259, 1409–1410.
[3]  Dubois, M.F.; Bensaude, O. MAP kinase activation during heat shock in quiescent and exponentially growing mammalian cells. FEBS Lett. 1993, 324, 191–195, doi:10.1016/0014-5793(93)81391-C.
[4]  Adler, V.; Schaffer, A.; Kim, J.; Dolan, L.; Ronai, Z. UV irradiation and heat shock mediate JNK activation via alternate pathways. J. Biol. Chem. 1995, 270, 26071–26077, doi:10.1074/jbc.270.44.26071.
[5]  Soti, C.; Pál, C.; Papp, B.; Csermely, P. Molecular chaperones as regulatory elements of cellular networks. Curr. Opin. Cell Biol. 2005, 17, 210–215, doi:10.1016/j.ceb.2005.02.012.
[6]  Xie, K.; Huang, S. Regulation of cancer metastasis by stress pathways. Clin. Exp. Metastasis 2003, 20, 31–43, doi:10.1023/A:1022590402748.
[7]  Santarosa, M.; Favaro, D.; Quaia, M.; Galligioni, E. Expression of heat shock protein 72 in renal cell carcinoma: Possible role and prognostic implications in cancer patients. Eur. J. Cancer 1997, 33, 873–877, doi:10.1016/S0959-8049(97)00002-6.
[8]  Nanbu, K.; Konishi, I.; Mandai, M.; Kuroda, H.; Hamid, A.A.; Komatsu, T.; Mori, T. Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Cancer Detect. Prev. 1998, 22, 549–555, doi:10.1046/j.1525-1500.1998.00069.x.
[9]  Mosser, D.D.; Morimoto, R.I. Molecular chaperones and the stress of oncogenesis. Oncogene 2004, 23, 2907–2918, doi:10.1038/sj.onc.1207529.
[10]  Whitesell, L.; Lindquist, S. Inhibiting the transcription factor HSF1 as an anticancer strategy. Expert Opin. Ther. Targets 2009, 13, 469–478, doi:10.1517/14728220902832697.
[11]  Powers, M.V.; Workman, P. Inhibitors of the heat shock response: Biology and pharmacology. FEBS Lett. 2007, 581, 3758–3769, doi:10.1016/j.febslet.2007.05.040.
[12]  Wigmore, S.J.; Sangster, K.; McNally, S.J.; Harrison, E.M.; Ross, J.A.; Fearon, K.C.H.; Garden, O.J. De-repression of heat shock transcription factor-1 in interleukin-6-treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3beta and MAPK/ERK-1. Int. J. Mol. Med. 2007, 19, 413–420.
[13]  Nylandsted, J.; Rohde, M.; Brand, K.; Bastholm, L.; Elling, F.; J??ttel?, M. Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2. Proc. Natl. Acad. Sci. USA 2000, 97, 7871–7876, doi:10.1073/pnas.97.14.7871.
[14]  Wei, Y.Q.; Zhao, X.; Kariya, Y.; Teshigawara, K.; Uchida, A. Inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein (HSP) 70 expression in tumor cells. Cancer Immunol. Immunother. 1995, 40, 73–78, doi:10.1007/BF01520287.
[15]  Kaur, J.; Kaur, J.; Ralhan, R. Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells. Int. J. Cancer J. Int. Cancer 2000, 85, 1–5, doi:10.1002/(SICI)1097-0215(20000101)85:1<1::AID-IJC1>3.0.CO;2-O.
[16]  J??ttel?, M. Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells. Int. J. Cancer 1995, 60, 689–693, doi:10.1002/ijc.2910600520.
[17]  Seo, J.S.; Park, Y.M.; Kim, J.I.; Shim, E.H.; Kim, C.W.; Jang, J.J.; Kim, S.H.; Lee, W.H. T cell lymphoma in transgenic mice expressing the human Hsp70 gene. Biochem. Biophys. Res. Commun. 1996, 218, 582–587, doi:10.1006/bbrc.1996.0103.
[18]  Volloch, V.Z.; Sherman, M.Y. Oncogenic potential of Hsp72. Oncogene 1999, 18, 3648–3651, doi:10.1038/sj.onc.1202525.
[19]  Gurbuxani, S.; Bruey, J.M.; Fromentin, A.; Larmonier, N.; Parcellier, A.; J??ttel?, M.; Martin, F.; Solary, E.; Garrido, C. Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. Oncogene 2001, 20, 7478–7485, doi:10.1038/sj.onc.1204948.
[20]  Ralhan, R.; Kaur, J. Differential expression of Mr 70,000 heat shock protein in normal, premalignant, and malignant human uterine cervix. Clin. Cancer Res. 1995, 1, 1217–1222.
[21]  Lazaris, A.C.; Theodoropoulos, G.E.; Aroni, K.; Saetta, A.; Davaris, P.S. Immunohistochemical expression of C-myc oncogene, heat shock protein 70 and HLA-DR molecules in malignant cutaneous melanoma. Virchows Arch. Int. J. Pathol. 1995, 426, 461–467.
[22]  Kaur, J.; Srivastava, A.; Ralhan, R. Expression of 70-kDa heat shock protein in oral lesions: Marker of biological stress or pathogenicity. Oral Oncol. 1998, 34, 496–501, doi:10.1016/S1368-8375(98)00064-5.
[23]  Syrigos, K.N.; Harrington, K.J.; Karayiannakis, A.J.; Sekara, E.; Chatziyianni, E.; Syrigou, E.I.; Waxman, J. Clinical significance of heat shock protein-70 expression in bladder cancer. Urology 2003, 61, 677–680, doi:10.1016/S0090-4295(02)02289-6.
[24]  Abe, M.; Manola, J.B.; Oh, W.K.; Parslow, D.L.; George, D.J.; Austin, C.L.; Kantoff, P.W. Plasma levels of heat shock protein 70 in patients with prostate cancer: A potential biomarker for prostate cancer. Clin. Prostate Cancer 2004, 3, 49–53, doi:10.3816/CGC.2004.n.013.
[25]  Chuma, M.; Sakamoto, M.; Yamazaki, K.; Ohta, T.; Ohki, M.; Asaka, M.; Hirohashi, S. Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology 2003, 37, 198–207, doi:10.1053/jhep.2003.50022.
[26]  Ciocca, D.R.; Clark, G.M.; Tandon, A.K.; Fuqua, S.A.; Welch, W.J.; McGuire, W.L. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: Prognostic implications. J. Natl. Cancer Inst. 1993, 85, 570–574, doi:10.1093/jnci/85.7.570.
[27]  Thanner, F.; Sütterlin, M.W.; Kapp, M.; Rieger, L.; Kristen, P.; Dietl, J.; Gassel, A.M.; Müller, T. Heat-shock protein 70 as a prognostic marker in node-negative breast cancer. Anticancer Res. 2003, 23, 1057–1062.
[28]  Thomas, X.; Campos, L.; Mounier, C.; Cornillon, J.; Flandrin, P.; Le, Q.-H.; Piselli, S.; Guyotat, D. Expression of heat-shock proteins is associated with major adverse prognostic factors in acute myeloid leukemia. Leuk. Res. 2005, 29, 1049–1058, doi:10.1016/j.leukres.2005.02.010.
[29]  Sun, X.F.; Zhang, H.; Carstensen, J.; Jansson, A.; Nordenskj?ld, B. Heat shock protein 72/73 in relation to cytoplasmic p53 expression and prognosis in colorectal adenocarcinomas. Int. J. Cancer 1997, 74, 600–604, doi:10.1002/(SICI)1097-0215(19971219)74:6<600::AID-IJC7>3.0.CO;2-Y.
[30]  Kawanishi, K.; Shiozaki, H.; Doki, Y.; Sakita, I.; Inoue, M.; Yano, M.; Tsujinaka, T.; Shamma, A.; Monden, M. Prognostic significance of heat shock proteins 27 and 70 in patients with squamous cell carcinoma of the esophagus. Cancer 1999, 85, 1649–1657, doi:10.1002/(SICI)1097-0142(19990415)85:8<1649::AID-CNCR2>3.0.CO;2-V.
[31]  Shiozaki, H.; Doki, Y.; Kawanishi, K.; Shamma, A.; Yano, M.; Inoue, M.; Monden, M. Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers. Surgery 2000, 127, 552–561, doi:10.1067/msy.2000.105028.
[32]  Maehara, Y.; Oki, E.; Abe, T.; Tokunaga, E.; Shibahara, K.; Kakeji, Y.; Sugimachi, K. Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer. Oncology 2000, 58, 144–151, doi:10.1159/000012091.
[33]  Nakajima, M.; Kato, H.; Miyazaki, T.; Fukuchi, M.; Masuda, N.; Fukai, Y.; Sohda, M.; Ahmad, F.; Kuwano, H. Tumor immune systems in esophageal cancer with special reference to heat-shock protein 70 and humoral immunity. Anticancer Res. 2009, 29, 1595–606.
[34]  Trieb, K.; Lechleitner, T.; Lang, S.; Windhager, R.; Kotz, R.; Dirnhofer, S. Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy. Hum. Pathol. 1998, 29, 1050–1055, doi:10.1016/S0046-8177(98)90412-9.
[35]  Multhoff, G.; Botzler, C.; Wiesnet, M.; Müller, E.; Meier, T.; Wilmanns, W.; Issels, R.D. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int. J. Cancer 1995, 61, 272–279, doi:10.1002/ijc.2910610222.
[36]  Multhoff, G.; Botzler, C.; Jennen, L.; Schmidt, J.; Ellwart, J.; Issels, R. Heat shock protein 72 on tumor cells: A recognition structure for natural killer cells. J. Immunol. 1997, 158, 4341–4350.
[37]  Gastpar, R.; Gehrmann, M.; Bausero, M.A.; Asea, A.; Gross, C.; Schroeder, J.A.; Multhoff, G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005, 65, 5238–5247, doi:10.1158/0008-5472.CAN-04-3804.
[38]  Korbelik, M.; Sun, J.; Cecic, I. Photodynamic therapy-induced cell surface expression and release of heat shock proteins: Relevance for tumor response. Cancer Res. 2005, 65, 1018–1026.
[39]  Asea, A.; Kraeft, S.K.; Kurt-Jones, E.A.; Stevenson, M.A.; Chen, L.B.; Finberg, R.W.; Koo, G.C.; Calderwood, S.K. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 2000, 6, 435–442, doi:10.1038/74697.
[40]  Garg, M.; Kanojia, D.; Saini, S.; Suri, S.; Gupta, A.; Surolia, A.; Suri, A. Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells. Cancer 2010, 116, 3785–3796, doi:10.1002/cncr.25218.
[41]  Simard, J.P.; Reynolds, D.N.; Kraguljac, A.P.; Smith, G.S.T.; Mosser, D.D. Overexpression of HSP70 inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells. J. Cell Sci. 2011, 124, 2367–2374, doi:10.1242/jcs.081745.
[42]  Chiu, C.-C.; Lin, C.-Y.; Lee, L.-Y.; Chen, Y.-J.; Lu, Y.-C.; Wang, H.-M.; Liao, C.-T.; Chang, J.T.-C.; Cheng, A.-J. Molecular Chaperones as a Common Set of Proteins That Regulate the Invasion Phenotype of Head and Neck Cancer. Clin. Cancer Res. 2011, 17, 4629–4641, doi:10.1158/1078-0432.CCR-10-2107.
[43]  Kluger, H.M.; Lev, D.C.; Kluger, Y.; McCarthy, M.M.; Kiriakova, G.; Camp, R.L.; Rimm, D.L.; Price, J.E. Using a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease. Cancer Res. 2005, 65, 5578–5587, doi:10.1158/0008-5472.CAN-05-0108.
[44]  Becker, B.; Multhoff, G.; Farkas, B.; Wild, P.-J.; Landthaler, M.; Stolz, W.; Vogt, T. Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases. Exp. Dermatol. 2004, 13, 27–32.
[45]  Gabai, V.L.; Yaglom, J.A.; Waldman, T.; Sherman, M.Y. Heat shock protein Hsp72 controls oncogene-induced senescence pathways in cancer cells. Mol. Cell. Biol. 2009, 29, 559–569, doi:10.1128/MCB.01041-08.
[46]  Gurbuxani, S.; Schmitt, E.; Cande, C.; Parcellier, A.; Hammann, A.; Daugas, E.; Kouranti, I.; Spahr, C.; Pance, A.; Kroemer, G.; Garrido, C. Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene 2003, 22, 6669–6678, doi:10.1038/sj.onc.1206794.
[47]  Rohde, M.; Daugaard, M.; Jensen, M.H.; Helin, K.; Nylandsted, J.; J??ttel?, M. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. Genes Dev. 2005, 19, 570–582.
[48]  Gabai, V.L.; Budagova, K.R.; Sherman, M.Y. Increased expression of the major heat shock protein Hsp72 in human prostate carcinoma cells is dispensable for their viability but confers resistance to a variety of anticancer agents. Oncogene 2005, 24, 3328–3338, doi:10.1038/sj.onc.1208495.
[49]  Wang, X.-P.; Wang, Q.-X.; Ying, X.-P. Correlation between clinicopathology and expression of heat shock protein 72 and glycoprotein 96 in human gastric adenocarcinoma. Tohoku J. Exp. Med. 2007, 212, 35–41, doi:10.1620/tjem.212.35.
[50]  Calderwood, S.K. Molecular Cochaperones: Tumor Growth and Cancer Treatment. Scientifica 2013, 2013, 1–13, doi:10.1155/2013/217513.
[51]  Dorsey, W.C.; Tchounwou, P.B. CYP1a1, HSP70, P53, and c-fos expression in human liver carcinoma cells (HepG2) exposed to pentachlorophenol. Biomed. Sci. Instrum. 2003, 39, 389–396.
[52]  Hwang, T.S.; Han, H.S.; Choi, H.K.; Lee, Y.J.; Kim, Y.-J.; Han, M.-Y.; Park, Y.-M. Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J. Gastroenterol. Hepatol. 2003, 18, 690–700, doi:10.1046/j.1440-1746.2003.03011.x.
[53]  Zorzi, E.; Bonvini, P. Inducible Hsp70 in the regulation of cancer cell survival: Analysis of chaperone induction, expression and activity. Cancers 2011, 3, 3921–3956, doi:10.3390/cancers3043921.
[54]  Fidler, I.J.; Nicolson, G.L. Fate of recirculating B16 melanoma metastatic variant cells in parabiotic syngeneic recipients. J. Natl. Cancer Inst. 1977, 58, 1867–1872.
[55]  Liotta, L.A.; Vembu, D.; Saini, R.K.; Boone, C. In vivo monitoring of the death rate of artificial murine pulmonary micrometastases. Cancer Res. 1978, 38, 1231–1236.
[56]  Wang, X.; Chen, W.; Li, X.; Lin, H.; Wang, Q. Heat shock protein 72 associated with CD44v6 in human colonic adenocarcinoma. Cell Biol. Int. 2008, 32, 860–864, doi:10.1016/j.cellbi.2008.02.009.
[57]  Ponta, H.; Sherman, L.; Herrlich, P.A. CD44: From adhesion molecules to signalling regulators. Nat. Rev. Mol. Cell Biol. 2003, 4, 33–45, doi:10.1038/nrm1004.
[58]  J??ttel?, M.; Wissing, D.; Bauer, P.A.; Li, G.C. Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. EMBO J. 1992, 11, 3507–3512.
[59]  J??ttel?, M.; Wissing, D.; Kokholm, K.; Kallunki, T.; Egeblad, M. Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases. EMBO J. 1998, 17, 6124–6134, doi:10.1093/emboj/17.21.6124.
[60]  J??ttel?, M.; Wissing, D. Heat-shock proteins protect cells from monocyte cytotoxicity: Possible mechanism of self-protection. J. Exp. Med. 1993, 177, 231–236, doi:10.1084/jem.177.1.231.
[61]  Simon, M.M.; Reikerstorfer, A.; Schwarz, A.; Krone, C.; Luger, T.A.; J??ttel?, M.; Schwarz, T. Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release. J. Clin. Invest. 1995, 95, 926–933, doi:10.1172/JCI117800.
[62]  Mosser, D.D.; Caron, A.W.; Bourget, L.; Denis-Larose, C.; Massie, B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol. Cell. Biol. 1997, 17, 5317–5327.
[63]  Buzzard, K.A.; Giaccia, A.J.; Killender, M.; Anderson, R.L. Heat shock protein 72 modulates pathways of stress-induced apoptosis. J. Biol. Chem. 1998, 273, 17147–17153, doi:10.1074/jbc.273.27.17147.
[64]  Vayssier, M.; Banzet, N.; Fran?ois, D.; Bellmann, K.; Polla, B.S. Tobacco smoke induces both apoptosis and necrosis in mammalian cells: Differential effects of HSP70. Am. J. Physiol. 1998, 275, L771–L779.
[65]  Nylandsted, J.; Gyrd-Hansen, M.; Danielewicz, A.; Fehrenbacher, N.; Lademann, U.; H?yer-Hansen, M.; Weber, E.; Multhoff, G.; Rohde, M.; J??ttel?, M. Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J. Exp. Med. 2004, 200, 425–435, doi:10.1084/jem.20040531.
[66]  Mosser, D.D.; Caron, A.W.; Bourget, L.; Meriin, A.B.; Sherman, M.Y.; Morimoto, R.I.; Massie, B. The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol. Cell. Biol. 2000, 20, 7146–7159, doi:10.1128/MCB.20.19.7146-7159.2000.
[67]  Gabai, V.L.; Meriin, A.B.; Mosser, D.D.; Caron, A.W.; Rits, S.; Shifrin, V.I.; Sherman, M.Y. Hsp70 prevents activation of stress Kinases a novel pathway of cellular thermotolerance. J. Biol. Chem. 1997, 272, 18033–18037, doi:10.1074/jbc.272.29.18033.
[68]  Park, H.-S.; Cho, S.-G.; Kim, C.K.; Hwang, H.S.; Noh, K.T.; Kim, M.-S.; Huh, S.-H.; Kim, M.J.; Ryoo, K.; Kim, E.K.; et al. Heat shock protein Hsp72 is a negative regulator of apoptosis signal-regulating Kinase 1. Mol. Cell. Biol. 2002, 22, 7721–7730, doi:10.1128/MCB.22.22.7721-7730.2002.
[69]  Park, H.-S.; Lee, J.-S.; Huh, S.-H.; Seo, J.-S.; Choi, E.-J. Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J. 2001, 20, 446–456, doi:10.1093/emboj/20.3.446.
[70]  Lee, J.-S.; Lee, J.-J.; Seo, J.-S. HSP70 Deficiency Results in Activation of c-Jun N-terminal Kinase, Extracellular Signal-regulated Kinase, and Caspase-3 in Hyperosmolarity-induced Apoptosis. J. Biol. Chem. 2005, 280, 6634–6641, doi:10.1074/jbc.M412393200.
[71]  Yaglom, J.; O’Callaghan-Sunol, C.; Gabai, V.; Sherman, M.Y. Inactivation of dual-specificity phosphatases is involved in the regulation of extracellular signal-regulated kinases by heat shock and hsp72. Mol. Cell. Biol. 2003, 23, 3813–3824, doi:10.1128/MCB.23.11.3813-3824.2003.
[72]  Song, J.; Takeda, M.; Morimoto, R.I. Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth. Nat. Cell Biol. 2001, 3, 276–282, doi:10.1038/35060068.
[73]  Yaglom, J.A.; Gabai, V.L.; Sherman, M.Y. High levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways. Cancer Res. 2007, 67, 2373–2381, doi:10.1158/0008-5472.CAN-06-3796.
[74]  Beere, H.M.; Wolf, B.B.; Cain, K.; Mosser, D.D.; Mahboubi, A.; Kuwana, T.; Tailor, P.; Morimoto, R.I.; Cohen, G.M.; Green, D.R. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat. Cell Biol. 2000, 2, 469–475, doi:10.1038/35019501.
[75]  Ravagnan, L.; Gurbuxani, S.; Susin, S.A.; Maisse, C.; Daugas, E.; Zamzami, N.; Mak, T.; J??ttel?, M.; Penninger, J.M.; Garrido, C.; et al. Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat. Cell Biol. 2001, 3, 839–843, doi:10.1038/ncb0901-839.
[76]  Doulias, P.-T.; Kotoglou, P.; Tenopoulou, M.; Keramisanou, D.; Tzavaras, T.; Brunk, U.; Galaris, D.; Angelidis, C. Involvement of heat shock protein-70 in the mechanism of hydrogen peroxide-induced DNA damage: The role of lysosomes and iron. Free Radic. Biol. Med. 2007, 42, 567–577, doi:10.1016/j.freeradbiomed.2006.11.022.
[77]  Schmitt, E.; Gehrmann, M.; Brunet, M.; Multhoff, G.; Garrido, C. Intracellular and extracellular functions of heat shock proteins: Repercussions in cancer therapy. J. Leukoc. Biol. 2007, 81, 15–27.
[78]  Felding-Habermann, B. Integrin adhesion receptors in tumor metastasis. Clin. Exp. Metastasis 2003, 20, 203–213, doi:10.1023/A:1022983000355.
[79]  Mehlen, P.; Puisieux, A. Metastasis: A question of life or death. Nat. Rev. Cancer 2006, 6, 449–458, doi:10.1038/nrc1886.
[80]  Gyrd-Hansen, M.; Nylandsted, J.; J??ttel?, M. Heat shock protein 70 promotes cancer cell viability by safeguarding lysosomal integrity. Cell Cycle 2004, 3, 1484–1485, doi:10.4161/cc.3.12.1287.
[81]  Jang, K.W.; Lee, J.E.; Kim, S.Y.; Kang, M.-W.; Na, M.H.; Lee, C.S.; Song, K.S.; Lim, S.P. The C-terminus of Hsp70-interacting protein promotes Met receptor degradation. J. Thorac. Oncol. 2011, 6, 679–687, doi:10.1097/JTO.0b013e31820d9c7e.
[82]  Mao, H.; Li, F.; Ruchalski, K.; Mosser, D.D.; Schwartz, J.H.; Wang, Y.; Borkan, S.C. Hsp72 inhibits focal adhesion kinase degradation in atp-depleted renal epithelial cells. J. Biol. Chem. 2003, 278, 18214–18220, doi:10.1074/jbc.M300126200.
[83]  Hofmann, U.B.; Houben, R.; Br?cker, E.-B.; Becker, J.C. Role of matrix metalloproteinases in melanoma cell invasion. Biochimie 2005, 87, 307–314, doi:10.1016/j.biochi.2005.01.013.
[84]  Abraham, R.; Sch?fer, J.; Rothe, M.; Bange, J.; Knyazev, P.; Ullrich, A. Identification of MMP-15 as an anti-apoptotic factor in cancer cells. J. Biol. Chem. 2005, 280, 34123–34132, doi:10.1074/jbc.M508155200.
[85]  Strand, S.; Vollmer, P.; van den Abeelen, L.; Gottfried, D.; Alla, V.; Heid, H.; Kuball, J.; Theobald, M.; Galle, P.R.; Strand, D. Cleavage of CD95 by matrix metalloproteinase-7 induces apoptosis resistance in tumour cells. Oncogene 2004, 23, 3732–3736, doi:10.1038/sj.onc.1207387.
[86]  Sims, J.D.; McCready, J.; Jay, D.G. Extracellular heat shock protein (Hsp)70 and Hsp90α assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS One 2011, 6, e18848, doi:10.1371/journal.pone.0018848.
[87]  Lee, K.-J.; Kim, Y.M.; Kim, D.Y.; Jeoung, D.; Han, K.; Lee, S.-T.; Lee, Y.-S.; Park, K.H.; Park, J.H.; Kim, D.J.; et al. Release of heat shock protein 70 (Hsp70) and the effects of extracellular Hsp70 on matric metalloproteinase-9 expression in human monocytic U937 cells. Exp. Mol. Med. 2006, 38, 364–374, doi:10.1038/emm.2006.43.
[88]  Cannito, S.; Novo, E.; Compagnone, A.; Valfrè di Bonzo, L.; Busletta, C.; Zamara, E.; Paternostro, C.; Povero, D.; Bandino, A.; Bozzo, F.; et al. Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis 2008, 29, 2267–2278, doi:10.1093/carcin/bgn216.
[89]  Zhong, Q.; Zhou, B.; Ann, D.K.; Minoo, P.; Liu, Y.; Banfalvi, A.; Krishnaveni, M.S.; Dubourd, M.; Demaio, L.; Willis, B.C.; et al. Role of endoplasmic reticulum stress in epithelial-mesenchymal transition of alveolar epithelial cells: Effects of misfolded surfactant protein. Am. J. Respir. Cell Mol. Biol. 2011, 45, 498–509, doi:10.1165/rcmb.2010-0347OC.
[90]  Can?z, O.; Belenli, O.; Patiroglu, T.E. General features of gastric carcinomas and comparison of HSP70 and NK cell immunoreactivity with prognostic factors. Pathol. Oncol. Res. 2002, 8, 262–269, doi:10.1007/BF03036742.
[91]  Teng, Y.; Ngoka, L.; Mei, Y.; Lesoon, L.; Cowell, J.K. HSP90 and HSP70 proteins are essential for stabilization and activation of WASF3 metastasis-promoting protein. J. Biol. Chem. 2012, 287, 10051–10059, doi:10.1074/jbc.M111.335000.
[92]  Birchmeier, C.; Birchmeier, W.; Gherardi, E.; vande Woude, G.F. Met, metastasis, motility and more. Nat. Rev. Mol. Cell Biol. 2003, 4, 915–925, doi:10.1038/nrm1261.
[93]  Li, Y.; Kang, X.; Wang, Q. HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal transition. J. Genet. Genomics 2011, 38, 111–116, doi:10.1016/j.jgg.2011.02.001.
[94]  Mao, H.; Wang, Y.; Li, Z.; Ruchalski, K.L.; Yu, X.; Schwartz, J.H.; Borkan, S.C. Hsp72 interacts with paxillin and facilitates the reassembly of focal adhesions during recovery from ATP depletion. J. Biol. Chem. 2004, 279, 15472–15480, doi:10.1074/jbc.M313484200.
[95]  Willmer, T.; Contu, L.; Blatch, G.L.; Edkins, A.L. Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines. Cancer Lett. 2013, 328, 252–260, doi:10.1016/j.canlet.2012.09.021.
[96]  Boroughs, L.K.; Antonyak, M.A.; Johnson, J.L.; Cerione, R.A. A unique role for heat shock protein 70 and its binding partner tissue transglutaminase in cancer cell migration. J. Biol. Chem. 2011, 286, 37094–37107, doi:10.1074/jbc.M111.242438.
[97]  Sossey-Alaoui, K.; Safina, A.; Li, X.; Vaughan, M.M.; Hicks, D.G.; Bakin, A.V.; Cowell, J.K. Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. Am. J. Pathol. 2007, 170, 2112–2121, doi:10.2353/ajpath.2007.060975.
[98]  Sossey-Alaoui, K.; Li, X.; Ranalli, T.A.; Cowell, J.K. WAVE3-mediated cell migration and lamellipodia formation are regulated downstream of phosphatidylinositol 3-Kinase. J. Biol. Chem. 2005, 280, 21748–21755, doi:10.1074/jbc.M500503200.
[99]  Teng, Y.; Ren, M.Q.; Cheney, R.; Sharma, S.; Cowell, J.K. Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases. Br. J. Cancer 2010, 103, 1066–1075, doi:10.1038/sj.bjc.6605850.
[100]  Iwasaki, M.; Homma, S.; Hishiya, A.; Dolezal, S.J.; Reed, J.C.; Takayama, S. BAG3 regulates motility and adhesion of epithelial cancer cells. Cancer Res. 2007, 67, 10252–10259, doi:10.1158/0008-5472.CAN-07-0618.
[101]  Suzuki, M.; Iwasaki, M.; Sugio, A.; Hishiya, A.; Tanaka, R.; Endo, T.; Takayama, S.; Saito, T. BAG3 (BCL2-associated athanogene 3) interacts with MMP-2 to positively regulate invasion by ovarian carcinoma cells. Cancer Lett. 2011, 303, 65–71, doi:10.1016/j.canlet.2011.01.019.
[102]  Song, X.; Wang, X.; Zhuo, W.; Shi, H.; Feng, D.; Sun, Y.; Liang, Y.; Fu, Y.; Zhou, D.; Luo, Y. The Regulatory mechanism of extracellular Hsp90α on matrix metalloproteinase-2 processing and tumor angiogenesis. J. Biol. Chem. 2010, 285, 40039–40049, doi:10.1074/jbc.M110.181941.
[103]  Walsh, N.; Larkin, A.; Swan, N.; Conlon, K.; Dowling, P.; McDermott, R.; Clynes, M. RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. Cancer Lett. 2011, 306, 180–189, doi:10.1016/j.canlet.2011.03.004.
[104]  Deryugina, E.I.; Quigley, J.P. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 2006, 25, 9–34, doi:10.1007/s10555-006-7886-9.
[105]  Leber, M.F.; Efferth, T. Molecular principles of cancer invasion and metastasis. Int. J. Oncol. 2009, 34, 881–895.
[106]  Chetty, C.; Vanamala, S.K.; Gondi, C.S.; Dinh, D.H.; Gujrati, M.; Rao, J.S. MMP-9 induces CD44 cleavage and CD44 mediated cell migration in glioblastoma xenograft cells. Cell. Signal. 2012, 24, 549–559, doi:10.1016/j.cellsig.2011.10.008.
[107]  Sherman, M.; Multhoff, G. Heat shock proteins in cancer. Ann. NY Acad. Sci. 2007, 1113, 192–201, doi:10.1196/annals.1391.030.
[108]  Arispe, N.; Doh, M.; Simakova, O.; Kurganov, B.; de Maio, A. Hsc70 and Hsp70 interact with phosphatidylserine on the surface of PC12 cells resulting in a decrease of viability. FASEB J. 2004, 18, 1636–1645, doi:10.1096/fj.04-2088com.
[109]  Arispe, N.; Doh, M.; de Maio, A. Lipid interaction differentiates the constitutive and stress-induced heat shock proteins Hsc70 and Hsp70. Cell Stress Chaperones 2002, 7, 330–338, doi:10.1379/1466-1268(2002)007<0330:LIDTCA>2.0.CO;2.
[110]  Bausero, M.A.; Gastpar, R.; Multhoff, G.; Asea, A. Alternative mechanism by which IFN-gamma enhances tumor recognition: Active release of heat shock protein 72. J. Immunol. 2005, 175, 2900–2912.
[111]  Broquet, A.H.; Thomas, G.; Masliah, J.; Trugnan, G.; Bachelet, M. Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J. Biol. Chem. 2003, 278, 21601–21606, doi:10.1074/jbc.M302326200.
[112]  Hunter-Lavin, C.; Davies, E.L.; Bacelar, M.M.F.V.G.; Marshall, M.J.; Andrew, S.M.; Williams, J.H.H. Hsp70 release from peripheral blood mononuclear cells. Biochem. Biophys. Res. Commun. 2004, 324, 511–517, doi:10.1016/j.bbrc.2004.09.075.
[113]  Lancaster, G.I.; Febbraio, M.A. Exosome-dependent trafficking of HSP70: A novel secretory pathway for cellular stress proteins. J. Biol. Chem. 2005, 280, 23349–23355, doi:10.1074/jbc.M502017200.
[114]  Mambula, S.S.; Calderwood, S.K. Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J. Immunol. 2006, 177, 7849–7857.
[115]  Lv, L.-H.; Wan, Y.-L.; Lin, Y.; Zhang, W.; Yang, M.; Li, G.-L.; Lin, H.-M.; Shang, C.-Z.; Chen, Y.-J.; Min, J. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro. J. Biol. Chem. 2012, 287, 15874–15885, doi:10.1074/jbc.M112.340588.
[116]  Radons, J.; Multhoff, G. Immunostimulatory functions of membrane-bound and exported heat shock protein 70. Exerc. Immunol. Rev. 2005, 11, 17–33.
[117]  Evdonin, A.L.; Guzhova, I.V.; Margulis, B.A.; Medvedeva, N.D. Extracellular heat shock protein 70 mediates heat stress-induced epidermal growth factor receptor transactivation in A431 carcinoma cells. FEBS Lett. 2006, 580, 6674–6678, doi:10.1016/j.febslet.2006.11.024.
[118]  Juhász, K.; Thuenauer, R.; Spachinger, A.; Duda, E.; Horváth, I.; Vígh, L.; Sonnleitner, A.; Balogi, Z. Lysosomal rerouting of Hsp70 trafficking as a potential immune activating tool for targeting melanoma. Curr. Pharm. Des. 2013, 19, 430–440, doi:10.2174/138161213804143644.
[119]  Petersen, N.H.T.; Kirkegaard, T.; Olsen, O.D.; J??ttel?, M. Connecting Hsp70, sphingolipid metabolism and lysosomal stability. Cell Cycle 2010, 9, 2305–2309, doi:10.4161/cc.9.12.12052.
[120]  Kurz, T.; Brunk, U.T. Autophagy of HSP70 and chelation of lysosomal iron in a non-redox-active form. Autophagy 2009, 5, 93–95, doi:10.4161/auto.5.1.7248.
[121]  Yang, Y.; Rao, R.; Shen, J.; Tang, Y.; Fiskus, W.; Nechtman, J.; Atadja, P.; Bhalla, K. Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion. Cancer Res. 2008, 68, 4833–4842, doi:10.1158/0008-5472.CAN-08-0644.
[122]  Kirkegaard, T.; Roth, A.G.; Petersen, N.H.T.; Mahalka, A.K.; Olsen, O.D.; Moilanen, I.; Zylicz, A.; Knudsen, J.; Sandhoff, K.; Arenz, C.; et al. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 2010, 463, 549–553, doi:10.1038/nature08710.
[123]  Fehrenbacher, N.; J??ttel?, M. Lysosomes as targets for cancer therapy. Cancer Res. 2005, 65, 2993–2995.
[124]  Vasiljeva, O.; Reinheckel, T.; Peters, C.; Turk, D.; Turk, V.; Turk, B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr. Pharm. Des. 2007, 13, 387–403, doi:10.2174/138161207780162962.
[125]  Joyce, J.A.; Baruch, A.; Chehade, K.; Meyer-Morse, N.; Giraudo, E.; Tsai, F.-Y.; Greenbaum, D.C.; Hager, J.H.; Bogyo, M.; Hanahan, D. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 2004, 5, 443–453, doi:10.1016/S1535-6108(04)00111-4.
[126]  Tu, C.; Ortega-Cava, C.F.; Chen, G.; Fernandes, N.D.; Cavallo-Medved, D.; Sloane, B.F.; Band, V.; Band, H. Lysosomal cathepsin B participates in the podosome-mediated extracellular matrix degradation and invasion via secreted lysosomes in v-Src fibroblasts. Cancer Res. 2008, 68, 9147–9156, doi:10.1158/0008-5472.CAN-07-5127.
[127]  Juhasz, K.; Lehner, M.; Hesse, J.; Haselgruebler, T.; Balogi, Z.; Center for Advanced Bioanalysis GmbH, Linz, Austria.. Unpublished work 2013.
[128]  Yano, Y.; Yano, A.; Oishi, S.; Sugimoto, Y.; Tsujimoto, G.; Fujii, N.; Matsuzaki, K. Coiled-coil tag—Probe system for quick labeling of membrane receptors in living cell. ACS Chem. Biol. 2008, 3, 341–345, doi:10.1021/cb8000556.
[129]  Vega, V.L.; Charles, W.; de Maio, A. A new feature of the stress response: Increase in endocytosis mediated by Hsp70. Cell Stress Chaperones 2010, 15, 517–527, doi:10.1007/s12192-009-0165-2.
[130]  Vega, V.L.; Rodriguez-Silva, M.; Frey, T.; Gehrmann, M.; Diaz, J.C.; Steinem, C.; Multhoff, G.; Arispe, N.; de Maio, A. Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J. Immunol. 2008, 180, 4299–4307.
[131]  Delneste, Y.; Magistrelli, G.; Gauchat, J.-F.; Haeuw, J.-F.; Aubry, J.-P.; Nakamura, K.; Kawakami-Honda, N.; Goetsch, L.; Sawamura, T.; Bonnefoy, J.-Y. Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 2002, 17, 353–362, doi:10.1016/S1074-7613(02)00388-6.
[132]  Thériault, J.R.; Mambula, S.S.; Sawamura, T.; Stevenson, M.A.; Calderwood, S.K. Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells. FEBS Lett. 2005, 579, 1951–1960, doi:10.1016/j.febslet.2005.02.046.
[133]  Basu, S.; Binder, R.J.; Ramalingam, T.; Srivastava, P.K. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 2001, 14, 303–313, doi:10.1016/S1074-7613(01)00111-X.
[134]  Thériault, J.R.; Adachi, H.; Calderwood, S.K. Role of scavenger receptors in the binding and internalization of heat shock protein 70. J. Immunol. 2006, 177, 8604–8611.
[135]  Bendz, H.; Ruhland, S.C.; Pandya, M.J.; Hainzl, O.; Riegelsberger, S.; Brauchle, C.; Mayer, M.P.; Buchner, J.; Issels, R.D.; Noessner, E. Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling. J. Biol. Chem. 2007, 282, 31688–31702, doi:10.1074/jbc.M704129200.
[136]  Noessner, E.; Gastpar, R.; Milani, V.; Brandl, A.; Hutzler, P.J.; Kuppner, M.C.; Roos, M.; Kremmer, E.; Asea, A.; Calderwood, S.K.; et al. Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J. Immunol. 2002, 169, 5424–5432.
[137]  Murshid, A.; Gong, J.; Calderwood, S.K. The role of heat shock proteins in antigen cross presentation. Front. Immunol. 2012, 3, 63.
[138]  Arnold-Schild, D.; Hanau, D.; Spehner, D.; Schmid, C.; Rammensee, H.G.; de la Salle, H.; Schild, H. Cutting edge: Receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells. J. Immunol. 1999, 162, 3757–3760.
[139]  Schild, H.; Arnold-Schild, D.; Lammert, E.; Rammensee, H.G. Stress proteins and immunity mediated by cytotoxic T lymphocytes. Curr. Opin. Immunol. 1999, 11, 109–113, doi:10.1016/S0952-7915(99)80019-3.
[140]  Enomoto, Y.; Bharti, A.; Khaleque, A.A.; Song, B.; Liu, C.; Apostolopoulos, V.; Xing, P.; Calderwood, S.K.; Gong, J. Enhanced immunogenicity of heat shock protein 70 peptide complexes from dendritic cell-tumor fusion cells. J. Immunol. 2006, 177, 5946–5955.
[141]  Stangl, S.; Gehrmann, M.; Riegger, J.; Kuhs, K.; Riederer, I.; Sievert, W.; Hube, K.; Mocikat, R.; Dressel, R.; Kremmer, E.; et al. Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc. Natl. Acad. Sci. USA 2011, 108, 733–738, doi:10.1073/pnas.1016065108.
[142]  Multhoff, G.; Pfister, K.; Gehrmann, M.; Hantschel, M.; Gross, C.; Hafner, M.; Hiddemann, W. A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity. Cell Stress Chaperones 2001, 6, 337–344, doi:10.1379/1466-1268(2001)006<0337:AMHPSN>2.0.CO;2.
[143]  Gross, C.; Schmidt-Wolf, I.G.; Nagaraj, S.; Gastpar, R.; Ellwart, J.; Kunz-Schughart, L.A.; Multhoff, G. Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells. Cell Stress Chaperones 2003, 8, 348–360, doi:10.1379/1466-1268(2003)008<0348:HSPRIA>2.0.CO;2.
[144]  Gastpar, R.; Gross, C.; Rossbacher, L.; Ellwart, J.; Riegger, J.; Multhoff, G. The cell surface-localized heat shock protein 70 epitope TKD induces migration and cytolytic activity selectively in human NK cells. J. Immunol. 2004, 172, 972–980.
[145]  Figueiredo, C.; Wittmann, M.; Wang, D.; Dressel, R.; Seltsam, A.; Blasczyk, R.; Eiz-Vesper, B. Heat shock protein 70 (HSP70) induces cytotoxicity of T-helper cells. Blood 2009, 113, 3008–3016, doi:10.1182/blood-2008-06-162727.
[146]  Clayton, A.; Turkes, A.; Navabi, H.; Mason, M.D.; Tabi, Z. Induction of heat shock proteins in B-cell exosomes. J. Cell Sci. 2005, 118, 3631–3638, doi:10.1242/jcs.02494.
[147]  Asea, A.; Rehli, M.; Kabingu, E.; Boch, J.A.; Bare, O.; Auron, P.E.; Stevenson, M.A.; Calderwood, S.K. Novel signal transduction pathway utilized by extracellular HSP70: Role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 2002, 277, 15028–15034, doi:10.1074/jbc.M200497200.
[148]  Vabulas, R.M.; Ahmad-Nejad, P.; Ghose, S.; Kirschning, C.J.; Issels, R.D.; Wagner, H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 2002, 277, 15107–15112, doi:10.1074/jbc.M111204200.
[149]  Basu, S.; Binder, R.J.; Suto, R.; Anderson, K.M.; Srivastava, P.K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int. Immunol. 2000, 12, 1539–1546, doi:10.1093/intimm/12.11.1539.
[150]  Panjwani, N.N.; Popova, L.; Srivastava, P.K. Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J. Immunol. 2002, 168, 2997–3003.
[151]  Sanchez-Perez, L.; Kottke, T.; Daniels, G.A.; Diaz, R.M.; Thompson, J.; Pulido, J.; Melcher, A.; Vile, R.G. Killing of normal melanocytes, combined with heat shock protein 70 and CD40L expression, cures large established melanomas. J. Immunol. 2006, 177, 4168–4177.
[152]  Wang, Y.; Whittall, T.; McGowan, E.; Younson, J.; Kelly, C.; Bergmeier, L.A.; Singh, M.; Lehner, T. Identification of stimulating and inhibitory epitopes within the heat shock protein 70 molecule that modulate cytokine production and maturation of dendritic cells. J. Immunol. 2005, 174, 3306–3316.
[153]  Kuppner, M.C.; Gastpar, R.; Gelwer, S.; N?ssner, E.; Ochmann, O.; Scharner, A.; Issels, R.D. The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors. Eur. J. Immunol. 2001, 31, 1602–1609, doi:10.1002/1521-4141(200105)31:5<1602::AID-IMMU1602>3.0.CO;2-W.
[154]  Chen, T.; Guo, J.; Han, C.; Yang, M.; Cao, X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J. Immunol. 2009, 182, 1449–1459.
[155]  Stocki, P.; Dickinson, A.M. The immunosuppressive activity of heat shock protein 70. Autoimmune Dis. 2012, 2012, 617213.
[156]  Van Eden, W.; Spiering, R.; Broere, F.; van der Zee, R. A case of mistaken identity: HSPs are no DAMPs but DAMPERs. Cell Stress Chaperones 2012, 17, 281–292, doi:10.1007/s12192-011-0311-5.
[157]  Henderson, B.; Calderwood, S.K.; Coates, A.R.M.; Cohen, I.; van Eden, W.; Lehner, T.; Pockley, A.G. Caught with their PAMPs down? The extracellular signalling actions of molecular chaperones are not due to microbial contaminants. Cell Stress Chaperones 2010, 15, 123–141, doi:10.1007/s12192-009-0137-6.
[158]  Tsan, M.-F.; Gao, B. Heat shock proteins and immune system. J. Leukoc. Biol. 2009, 85, 905–910, doi:10.1189/jlb.0109005.
[159]  Calderwood, S.K.; Murshid, A.; Gong, J. Heat shock proteins: Conditional mediators of inflammation in tumor immunity. Front. Immunol. 2012, 3, 75.
[160]  Multhoff, G.; Molls, M.; Radons, J. Chronic inflammation in cancer development. Front. Immunol. 2011, 2, 98.
[161]  Wachstein, J.; Tischer, S.; Figueiredo, C.; Limbourg, A.; Falk, C.; Immenschuh, S.; Blasczyk, R.; Eiz-Vesper, B. HSP70 enhances immunosuppressive function of CD4(+)CD25(+)FoxP3(+) T regulatory cells and cytotoxicity in CD4(+)CD25(?) T cells. PLoS One 2012, 7, e51747, doi:10.1371/journal.pone.0051747.
[162]  Chalmin, F.; Ladoire, S.; Mignot, G.; Vincent, J.; Bruchard, M.; Remy-Martin, J.-P.; Boireau, W.; Rouleau, A.; Simon, B.; Lanneau, D.; et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest. 2010, 120, 457–471.
[163]  Van Eden, W.; van der Zee, R.; Prakken, B. Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat. Rev. Immunol. 2005, 5, 318–330, doi:10.1038/nri1593.
[164]  Borges, T.J.; Wieten, L.; van Herwijnen, M.J.; Broere, F.; van der Zee, R.; Bonorino, C.; van Eden, W. The anti-inflammatory mechanisms of Hsp70. Front. Immunol. 2012, 3, 95.
[165]  Stocki, P.; Wang, X.N.; Dickinson, A.M. Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells. J. Biol. Chem. 2012, 287, 12387–12394, doi:10.1074/jbc.M111.307579.
[166]  Evdonin, A.L.; Kropacheva, I.V.; Medvedeva, N.D. Extracellular Hsp70 stimulates multiple signaling pathways in A431 carcinoma cells. Biochem. Mosc. Suppl. Ser. A Membr. Cell Biol. 2009, 3, 291–297, doi:10.1134/S1990747809030088.
[167]  Ellerbroek, S.M.; Hudson, L.G.; Stack, M.S. Proteinase requirements of epidermal growth factor-induced ovarian cancer cell invasion. Int. J. Cancer 1998, 78, 331–337, doi:10.1002/(SICI)1097-0215(19981029)78:3<331::AID-IJC13>3.0.CO;2-9.
[168]  Jijon, H.B.; Buret, A.; Hirota, C.L.; Hollenberg, M.D.; Beck, P.L. The EGF receptor and HER2 participate in TNF-α-dependent MAPK activation and IL-8 secretion in intestinal epithelial cells. Mediators Inflamm. 2012, 2012, 207398.
[169]  Wells, A. Tumor invasion: Role of growth factor-induced cell motility. Adv. Cancer Res. 2000, 78, 31–101, doi:10.1016/S0065-230X(08)61023-4.
[170]  Wu, F.-H.; Yuan, Y.; Li, D.; Liao, S.-J.; Yan, B.; Wei, J.-J.; Zhou, Y.-H.; Zhu, J.-H.; Zhang, G.-M.; Feng, Z.-H. Extracellular HSPA1A promotes the growth of hepatocarcinoma by augmenting tumor cell proliferation and apoptosis-resistance. Cancer Lett. 2012, 317, 157–164, doi:10.1016/j.canlet.2011.11.020.
[171]  Gong, W.; Wang, Z.-Y.; Chen, G.-X.; Liu, Y.-Q.; Gu, X.-Y.; Liu, W.-W. Invasion potential of H22 hepatocarcinoma cells is increased by HMGB1-induced tumor NF-κB signaling via initiation of HSP70. Oncol. Rep. 2013, doi:10.3892/or.2013.2595.
[172]  Ellerman, J.E.; Brown, C.K.; de Vera, M.; Zeh, H.J.; Billiar, T.; Rubartelli, A.; Lotze, M.T. Masquerader: High mobility group box-1 and cancer. Clin. Cancer Res. 2007, 13, 2836–2848, doi:10.1158/1078-0432.CCR-06-1953.
[173]  Klink, M.; Nowak, M.; Kielbik, M.; Bednarska, K.; Blus, E.; Szpakowski, M.; Szyllo, K.; Sulowska, Z. The interaction of HspA1A with TLR2 and TLR4 in the response of neutrophils induced by ovarian cancer cells in vitro. Cell Stress Chaperones 2012, 17, 661–674, doi:10.1007/s12192-012-0338-2.
[174]  Ushio-Fukai, M.; Alexander, R.W. Reactive oxygen species as mediators of angiogenesis signaling: Role of NAD(P)H oxidase. Mol. Cell. Biochem. 2004, 264, 85–97, doi:10.1023/B:MCBI.0000044378.09409.b5.
[175]  De Larco, J.E.; Wuertz, B.R.K.; Furcht, L.T. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin. Cancer Res. 2004, 10, 4895–4900, doi:10.1158/1078-0432.CCR-03-0760.
[176]  Wheeler, D.S.; Chase, M.A.; Senft, A.P.; Poynter, S.E.; Wong, H.R.; Page, K. Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4. Respir. Res. 2009, 10, 31, doi:10.1186/1465-9921-10-31.
[177]  Becker, T.; Hartl, F.-U.; Wieland, F. CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J. Cell Biol. 2002, 158, 1277–1285, doi:10.1083/jcb.200208083.
[178]  Wang, Y.; Kelly, C.G.; Karttunen, J.T.; Whittall, T.; Lehner, P.J.; Duncan, L.; MacAry, P.; Younson, J.S.; Singh, M.; Oehlmann, W.; et al. CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 2001, 15, 971–983, doi:10.1016/S1074-7613(01)00242-4.
[179]  Van Kooten, C.; Banchereau, J. CD40-CD40 ligand. J. Leukoc. Biol. 2000, 67, 2–17.
[180]  Futagami, S.; Hiratsuka, T.; Shindo, T.; Hamamoto, T.; Horie, A.; Ueki, N.; Kusunoki, M.; Gudis, K.; Miyake, K.; Tsukui, T.; et al. Extracellular HSP70 blocks CD40L-induced apoptosis and tubular formation in endothelial cells. J. Gastroenterol. Hepatol. 2008, 23, S222–S228, doi:10.1111/j.1440-1746.2008.05442.x.
[181]  Zhan, R.; Leng, X.; Liu, X.; Wang, X.; Gong, J.; Yan, L.; Wang, L.; Wang, Y.; Wang, X.; Qian, L.-J. Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes. Biochem. Biophys. Res. Commun. 2009, 387, 229–233, doi:10.1016/j.bbrc.2009.06.095.
[182]  Peinado, H.; Ale?kovi?, M.; Lavotshkin, S.; Matei, I.; Costa-Silva, B.; Moreno-Bueno, G.; Hergueta-Redondo, M.; Williams, C.; García-Santos, G.; Ghajar, C.; et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 2012, 18, 883–891, doi:10.1038/nm.2753.
[183]  Goloudina, A.R.; Demidov, O.N.; Garrido, C. Inhibition of HSP70: A challenging anti-cancer strategy. Cancer Lett. 2012, 325, 117–124, doi:10.1016/j.canlet.2012.06.003.
[184]  Murshid, A.; Gong, J.; Stevenson, M.A.; Calderwood, S.K. Heat shock proteins and cancer vaccines: Developments in the past decade and chaperoning in the decade to come. Expert Rev. Vaccines 2011, 10, 1553–1568, doi:10.1586/erv.11.124.
[185]  Ciocca, D.R.; Cayado-Gutierrez, N.; Maccioni, M.; Cuello-Carrion, F.D. Heat shock proteins (HSPs) based anti-cancer vaccines. Curr. Mol. Med. 2012, 12, 1183–1197, doi:10.2174/156652412803306684.
[186]  Garg, M.; Kanojia, D.; Seth, A.; Kumar, R.; Gupta, A.; Surolia, A.; Suri, A. Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion. Eur. J. Cancer 2010, 46, 207–215, doi:10.1016/j.ejca.2009.10.020.
[187]  Du, X.L.; Jiang, T.; Wen, Z.Q.; Gao, R.; Cui, M.; Wang, F. Silencing of heat shock protein 70 expression enhances radiotherapy efficacy and inhibits cell invasion in endometrial cancer cell line. Croat. Med. J. 2009, 50, 143–150, doi:10.3325/cmj.2009.50.143.
[188]  Weber, G.F. Why does cancer therapy lack effective anti-metastasis drugs? Cancer Lett. 2013, 328, 207–211, doi:10.1016/j.canlet.2012.09.025.
[189]  Weng, D.; Penzner, J.H.; Song, B.; Koido, S.; Calderwood, S.K.; Gong, J. Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers. Breast Cancer Res. 2012, 14, R18, doi:10.1186/bcr3102.
[190]  Botzler, C.; Issels, R.; Multhoff, G. Heat-shock protein 72 cell-surface expression on human lung carcinoma cells in associated with an increased sensitivity to lysis mediated by adherent natural killer cells. Cancer Immunol. Immunother. 1996, 43, 226–230, doi:10.1007/s002620050326.
[191]  Stangl, S.; Wortmann, A.; Guertler, U.; Multhoff, G. Control of metastasized pancreatic carcinomas in SCID/beige mice with human IL-2/TKD-activated NK cells. J. Immunol. 2006, 176, 6270–6276.
[192]  Botzler, C.; Schmidt, J.; Luz, A.; Jennen, L.; Issels, R.; Multhoff, G. Differential Hsp70 plasma-membrane expression on primary human tumors and metastases in mice with severe combined immunodeficiency. Int. J. Cancer 1998, 77, 942–948, doi:10.1002/(SICI)1097-0215(19980911)77:6<942::AID-IJC25>3.0.CO;2-1.
[193]  Multhoff, G.; Pfister, K.; Botzler, C.; Jordan, A.; Scholz, R.; Schmetzer, H.; Burgstahler, R.; Hiddemann, W. Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors. Int. J. Cancer 2000, 88, 791–797, doi:10.1002/1097-0215(20001201)88:5<791::AID-IJC17>3.0.CO;2-I.
[194]  Moser, C.; Schmidbauer, C.; Gürtler, U.; Gross, C.; Gehrmann, M.; Thonigs, G.; Pfister, K.; Multhoff, G. Inhibition of tumor growth in mice with severe combined immunodeficiency is mediated by heat shock protein 70 (Hsp70)-peptide-activated, CD94 positive natural killer cells. Cell Stress Chaperones 2002, 7, 365–373, doi:10.1379/1466-1268(2002)007<0365:IOTGIM>2.0.CO;2.
[195]  Krause, S.W.; Gastpar, R.; Andreesen, R.; Gross, C.; Ullrich, H.; Thonigs, G.; Pfister, K.; Multhoff, G. Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: A clinical phase i trial. Clin. Cancer Res. 2004, 10, 3699–3707, doi:10.1158/1078-0432.CCR-03-0683.
[196]  Milani, V.; Stangl, S.; Issels, R.; Gehrmann, M.; Wagner, B.; Hube, K.; Mayr, D.; Hiddemann, W.; Molls, M.; Multhoff, G. Anti-tumor activity of patient-derived NK cells after cell-based immunotherapy—A case report. J. Transl. Med. 2009, 7, 50, doi:10.1186/1479-5876-7-50.
[197]  Gehrmann, M.; Stangl, S.; Kirschner, A.; Foulds, G.A.; Sievert, W.; Doss, B.T.; Walch, A.; Pockley, A.G.; Multhoff, G. Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B. PLoS One 2012, 7, e41341, doi:10.1371/journal.pone.0041341.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133

WeChat 1538708413