%0 Journal Article
%T Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer
%A Farbod Shojaei
%A Nathan Scott
%A Xiaolin Kang
%A Patrick B Lappin
%A Amanda A Fitzgerald
%A Shannon Karlicek
%A Brett H Simmons
%A Aidong Wu
%A Joseph H Lee
%A Simon Bergqvist
%A Eugenia Kraynov
%J Journal of Experimental & Clinical Cancer Research
%D 2012
%I BioMed Central
%R 10.1186/1756-9966-31-26
%X OPN is a multifunctional protein involved in several pathological processes such as inflammation and cancer [1]. As an acidic glycophosphoprotein, OPN contains a RGD (arginine-glycine-aspartate) integrin binding motif, a hydrophobic leader sequence (indicative of its secretory characteristic), a thrombin cleavage site adjacent to RGD domain, and a cell attachment sequence [2]. OPN has been found to be present in three forms in tissues and fluids: i) an intracellular protein in complex with hyaluronan-CD44-ERM (ezrin/radixin/moesin) that is involved in migration of tumor and stromal cells [3]; ii) an extracellular protein that is abundant at mineralized tissues [4]; iii) a secreted protein that is found in fluids isolated from metastatic tumors [5] and also found in organs such as placenta [6,7], breast [8], and testes [9]. At the protein synthesis level, OPN undergoes extensive post-translational modification including phosphorylation and glycosylation [10]. Additionally, there are three splice variants of OPN (OPNa, OPNb, and OPNc) that may have distinct characteristics in different tissues and tumor types [11]. For example, OPN-c has been suggested to be expressed in invasive breast tumors and is highly correlated with patient's survival in HER-2 breast patients [12]. Irrespective of OPN isoform, a series of other studies have suggested a role for plasma OPN as a biomarker of tumor progression in colon [13,14], lung [15], and prostate cancers [16,17].The RGD sequence in OPN protein enables it to bind to CD44-ERM and several integrins including ¦ÁV¦Â1, ¦Áv¦Â3, and ¦ÁV¦Â5 [18]. Given the wide expression of integrins and CD44, both cancer cells as well as stromal compartment are targeted by OPN in the tumor mass. Binding of OPN to the above receptors on tumor cells triggers downstream signaling pathways including Ras, Akt, MAPK, Src, FAK and NF-KB [1] that collectively lead to the following in tumor cells: i) invasion to ECM (extracellular matrix) mainly via upregulation o
%U http://www.jeccr.com/content/31/1/26