Oct 14: Dissecting human prostate cancer cell heterogeneity
Speaker：Dean G. Tang, The University of Texas M.D Anderson Cancer Center, Department of Molecular Carcinogenesis, Science Park, Smithville, TX
When: 2013-10-14 13:30
Where: Conference Room 534, School of Life Sciences
Abstract: Cancer stem cells (CSCs) have been reported in multiple human and model tumor systems. The reported CSCs are phenotypically diverse and functionally unique in that they possess inherent resistance to many anti-cancer therapeutics. CSCs are not fixed cell populations; rather, non-stem cancer cells can be turned into CSCs by microenvironmental changes such as hypoxia, increased acidity, and inflammatory signals. Working on prostate cancer (PCa), we have shown that the undifferentiated (i.e., PSA-/lo) PCa cell population harbors self-renewing long-term tumor-propagating cells that fulfill all criteria that define CSCs: they can undergo authentic asymmetric cell division generating more differentiated (PSA+) PCa cells; they overexpress dozens of stem cell-associated genes; they possess epigenetic profiles characteristic of normal stem cells; they are largely quiescent but can be mobilized into the cell cycle; and they possess indefinite tumor-propagating activity in androgen-proficient male animals. Important, the PSA-/lo PCa cells are intrinsically refractory to standard-of-care chemotherapy and androgen-deprivation therapy. Moreover, the PSA-/lo PCa cells manifest high tumor-regenerating activity in fully castrated hosts and can mediate tumor recurrence upon failure of castration. Furthermore, PCa cells with high metastatic potential are greatly enriched for CSC phenotypes and functions. The PSA-/lo prostate CSC (PCSC) pool is heterogeneous in that only ~5-20% of the cells can undergo asymmetric cell division and that it contains many other subsets of more tumorigenic cells. The PSA+ PCa cells are plastic in that constitutive overexpression of Nanog or persistent castration in vitro and in vivo can induce their de-differentiation. The heterogeneity in PCSCs and the plasticity of non-PCSCs suggest that novel therapeutics specifically targeting PCSCs need to be developed and used in conjunction with the current standard and targeted treatment modalities to prevent tumor recurrence and distant metastasis.