Identification of cancer stem cell properties in the human cell line IGR-CaP1, established from a localized epithelial prostate cancer

ANNE CHAUCHEREAU, CATHERINE GAUDIN, NADER AL NAKOUZI, DANIEL COMPAGNO, PAULE OPOLON, ELISABETH CONNAULT, NATHALIE AUGER, PATRICK GONIN, SYLVESTRE LE MOULEC, CHRISTOPHE MASSARD, AND KARIM FIZAZI

EE.UU

Congreso; AACR; 2008

Deciphering molecular pathways involved in early steps of the prostate oncogenesis requires both in vitro and in vivo models derived from human primary tumors. However the few recognized models of human prostate epithelial cancer originate from metastases; so far a very few models from primary tumor are proposed. Immortalization of normal human prostate cells (epithelial or stromal) does not recapitulate natural history of the disease. By culturing human prostate primary tumor cells onto a human epithelial extra-cellular matrix, we have successfully selected a new prostate cancer cell line, IGR-CaP1, and clonally-derived subclones. IGR-CaP1 cells that harbor a tetraploid karyotype, high telomerase activity and mutated TP53 rapidly induce subcutaneous xenografts in nude mice. Orthotopic injection of IGR-CaP1 cells yields an undifferentiated prostate adenocarcinoma able to metastasize in liver and lung of the animals. Furthermore, IGR-CaP1 cell lines, all negative for androgen receptor and PSA, express the prostate basal epithelial markers CK5 and CK14. More importantly, these clones express high levels of CD44, CD133, and CXCR4 associated with a high expression of a2b1-integrin and the transcription factor Oct4 that are reported as prostate cancer stemness markers. RT-PCR data also pointed out high activation of Sonic Hedgehog signalling pathway in these cells. As a result, the hormone-independent IGR-CaP1 cellular clones exhibit original features of both basal prostate tissue and cancer stemness. Tumorigenic IGR-CaP1 clones constitute invaluable human models for studying prostate cancer progression and drug assessment in vitro as well as in animals specifically for developing new therapeutic approaches targeting prostate cancer stem cells. Keywords: primary tumor, human prostate cancer cell line; basal epithelial cells; stemness gene markers