Abstract
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.
Highlights
While the cellular origin of cancer remains unresolved, two long-time competing hypotheses, namely the “stem cell theory” [1] and the “de-differentiation theory” of cancer [2], have enticed new interest because of recent advances in stem cell research and molecular oncology
Using conditions that favor the clonal expansion of cancer stem cells, we have found that the expression of all three potential cancer stem cell markers raised initially in both the highly tumorigenic prostate cancer cell line PC3, and the weakly malignant prostate cancer cell line LNCaP, but decreased thereafter presumably as a consequence of a partial cell differentiation, in accordance to the results of previous studies on other cell model systems [45]
In this study we have investigated the expression of both presumptive cancer stem cell markers and cell differentiation markers in two established human prostate cancer cells, LNCaP and PC3, aiming to define molecular profiles of potential cancer stem and cancer non-stem cells within either cell line
Summary
While the cellular origin of cancer remains unresolved, two long-time competing hypotheses, namely the “stem cell theory” [1] and the “de-differentiation theory” of cancer [2], have enticed new interest because of recent advances in stem cell research and molecular oncology. The ideas that cancer is a “disease of cell differentiation” [4], a “stem cell disease” [5] and “oncogeny as partially-blocked ontogeny” [6] depend on the original target cell, that leads to cancer, being an adult stem cell. Even though each tumor contains genotypic/phenotypic–diverse cells, they all seem to have originated from a single “cancer stem cell”, in that they are clonally-derived [7,8]. Adult human stem cells have been isolated or identified from human kidney [17,18], breast [19], pancreas [20], mesenchyme [21], liver [22] and prostate [23,24,25]
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