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Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

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Technical Report,13 Sep 2014,12 Sep 2015

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The University of Texas MD Anderson Cancer Center Houston United States

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Prostate cancer PCa metastasis represents the worst outcome that eventually kills the patient. Although many PCa cell-intrinsic molecules and end-organ factors have been implicated in the metastatic dissemination of PCa cells, the role of primary tumor microenvironment and the nature of the metastatic PCa cells remain poorly defined. By establishing a reliable and quantifiable experimental PCa metastasis model in NODSCID mice, we have found that PCa cells implanted orthotopically i.e., in the prostatemetastasize much more extensively and widely than those implanted ectopically i.e., subcutaneously or s.c. Microarray-based gene expression profiling reveals that the orthotopically implanted human PCa cells upregulate several classes of genes that have been intimately implicated in metastasis. These and many other preliminary observations allow us to HYPOTHESIZE that PCa cells reciprocally interact with the host cells to establish a proinflammatory microenvironment highly conducive to PCa metastasis and that metastatic PCa cells are endowed with CSC properties. By the end of the second year, we have largely accomplished whats initially proposed in Aims 1 and 2 with relevant manuscripts are under preparation now. The final year will be dedicated to Aim 3, whose is focus is on elucidating the signaling mechanisms that promote PCa cell metastasis

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