Low PSA Prostate Cancer Cells Solve the Mystery of Castrate Resistance

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(ChemotherapyAdvisor) – Prostate-cancer cell populations that either produce no prostate-specific antigen (PSA) or produce low levels of PSA may represent a critical source of castration-resistant cells, according to a multinational team of investigators. The researchers wrote this conclusion in a paper entitled “The PSA−/lo Prostate Cancer Cell Population Harbors Self-Renewing Long-Term Tumor-Propagating Cells that Resist Castration,” which was published in Cell Stem Cell on May 4.

In this study, the researchers described the heterogeneous nature of prostate cancer, which is characterized by the presence of both differentiated and undifferentiated tumor cells. An investigation into the respective functions of each cell population in the tumor, which has not been well characterized to date, was undertaken. Here, the investigators report “distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (PSA+) and low (PSA−/lo) levels of the differentiation marker PSA.”

The investigators reported that the PSA–/lo prostate cancer cell population is quiescent, refractory to stresses (including androgen deprivation), capable of initiating robust tumor development, resistant to androgen ablation in castrated hosts, and harbors highly tumorigenic castration-resistant prostate cancer cells. PSA-positive prostate cancer cells possess more limited tumor-propagating capacity, undergo symmetric division, and are sensitive to castration, the investigators wrote.

The authors also commented that the pattern observed in these cell lines and in a mouse model of prostate cancer closely resemble progression observed in patients after androgen-deprivation treatment, and thus reflect reduced PSA-producing cells in patient tumors after androgen depletion.

The investigators concluded: “PSA−/lo cells may represent a critical source of castration-resistant PCa cells.”


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