Defining two populations of prostate cancer cells with distinct molecular, biological, and tumor-propagating properties Conference Paper uri icon

abstract

  • Abstract Prostate cancer (PCa) is a heterogeneous malignancy containing different types of tumor cells. The cellular basis underlying PCa cell heterogeneity and functional importance of different PCa cell populations in maintaining tumor homeostasis and mediating castration-resistant progression remain poorly understood. By whole-genome microarray analysis, time-lapse videomicroscopy, serial tumor transplantations, and other functional assays, here we report the distinct molecular, cell biological, and tumor-propagating properties of PCa cells that express high (i.e., PSA+) and low (PSA/lo) levels of PSA. PSA/lo PCa cells are relatively quiescent and resistant to multiple stresses, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity in intact male mice. They preferentially express stem cell-associated genes and epigenetic profiles and can generate PSA+ cells by either asymmetric or symmetric cell division. Of great clinic significance, PSA/lo PCa cells can initiate robust tumor development in fully castrated hosts and survive experimental androgen-deprivation therapy. In contrast, PSA+ PCa cells, despite being highly tumorigenic in androgen-proficient hosts, possess more limited tumor-propagating capacity, mainly undergo symmetric division, and are sensitive to castration. Our data together suggest that the two populations of PCa cells appear to play differential roles in tumor maintenance and PSA/lo cells may represent an important source of castration-resistant PCa cells. Our findings have important implications in understanding PCa cell heterogeneity, tumor response to the mainstay antiandrogen therapies, and emergence of castration-resistant PCa. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 476. doi:10.1158/1538-7445.AM2011-476

published proceedings

  • CANCER RESEARCH

author list (cited authors)

  • Qin, J., Liu, X., Laffin, B., Chen, X., Choy, G., Jeter, C., ... Tang, D. G.

citation count

  • 0

complete list of authors

  • Qin, Jichao||Liu, Xin||Laffin, Brian||Chen, Xin||Choy, Grace||Jeter, Collene||Calhoun-Davis, Tammy||Li, Hangwen||Ivanov, Ivan||Palapattu, Ganesh||Pang, Shen||Huang, Jiaoti||Suraneni, Mahipal||Tang, Dean G

publication date

  • January 1, 2011 11:11 AM