Jornal de pesquisa e terapia com células-tronco

Abstrato

Molecular Profiling of Potential Human Prostate Cancer Stem Cells

Vitale Miceli, Letizia Cocciadiferro, Zarcone Maurizio, Kyung-Sun Kang, James E. Trosko and Giuseppe Carruba

We have investigated the expression of Oct-4, Suz-12, and Cripto-1, as presumptive “stemness” genes, and of connexin 43 (Cx43), Cx32 and androgen receptor (AR), as cell differentiation genes, in two human prostate cancer cell lines, PC3 and LNCaP. This aiming to define molecular profiles of prostate cancer stem cells for a better understanding of prostate carcinogenesis and tumor progression, as well as for prognostic or therapeutic purposes. Cells were grown in 3-dimensional (3D) cell cultures to favor clonal expansion of cancer stem and early progenitor cells, and compared to cells grown in 2-dimensional (2D) cell cultures. Under 3D culture conditions, LNCaP cells and PC3 cells generated cell spheroids and aggregates, respectively. Under this condition, the expression of candidate stemness genes markedly increased with respect to 2D cell cultures up to day 4 of culture but drastically fell thereafter, while connexin genes gradually decreased up to day 6, where upon, a rise of AR transcript could be observed. Our data suggest that Oct-4+/Suz-12+/Cripto-1+ cells represent human prostate cancer stem or early progenitor cells and that this molecular profile could be used to screen several tumor promoters and/or chemotherapeutic agents, to obtain prognostic indication and to predict response of patients to treatment.