%0 Journal Article
%T Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments
%A Balaji Krishnamachary
%A Flonne Wildes
%A Marie-France Penet
%A Pierre Danhier
%A Samata Kakkad
%A Santosh Kumar Bharti
%A Zaver M. Bhujwalla
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2019
%R 10.1016/j.neo.2018.12.004
%X Metastatic dissemination continues to be a major cause of prostate cancer (PCa) mortality, creating a compelling need to understand factors that play a role in the metastatic cascade. Since hypoxia plays an important role in PCa aggressiveness, we characterized patterns of hypoxia in the primary tumor and metastatic environments of a human PCa xenograft. We previously developed and characterized an imaging strategy based on the hypoxia response element (HRE)¨Cdriven expression of long-lived enhanced green fluorescent protein (EGFP) and short-lived luciferase (luc) fused to the oxygen-dependent degradation domain in human PCa PC-3 cells. Both reporter proteins were placed under the transcriptional control of a five¨Ctandem repeat HRE sequence. PC-3 cells also constitutively expressed the tdTomato red fluorescent protein, allowing cancer cell detection in vivo. This ˇ°timerˇ± strategy can provide information on the temporal evolution of HIF activity and hypoxia in tumors. Here, for the first time, we performed in vivo and ex vivo imaging of this dual HIF reporter system in PC-3 metastatic tumors implanted orthotopically in the prostate and PC-3 nonmetastatic tumors implanted subcutaneously. We observed distinct patterns of EGFP and luc expression in subcutaneous and orthotopic tumors, and in metastatic nodules, that provide new insights into the presence of hypoxia at primary and metastatic tumor sites, and of the role of hypoxia in metastasis
%K BLI
%K bioluminescence imaging
%K EGFP
%K enhanced green fluorescent protein
%K HIF
%K hypoxia inducible factor
%K HRE
%K hypoxia response element
%K Luc
%K luciferase
%K ODD
%K oxygen-dependent degradation domain
%K PCa
%K prostate cancer
%K RFP
%K red fluorescent protein
%K SEM
%K standard error of the mean
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327878/