Prostate cancer stem cells 41 Origin of PCSCs

The origin of PCSCs continues to stay as a controversial issue. Different cells in origin may generate clinically relevant subtypes with different prognosis and outcome. There are two possible cell origin resources in PC: the basal and luminal cell-of-origin.

4.1.1. Basal cell-of-origin

Much stronger studies came from several independent laboratories that used different PC models to support the view that basal stem cells provide the cell-of-origin for PC. When CD49fhiTrop2hi cells were selected from the basal fraction, transfected with Akt/Erg vectors and transplanted to induce initiation of prostatic intraepithelial neoplasia [57]; these basal cells derived from primary benign human prostate tissue initiated PC in immunodeficient mice [24]. It was also reported that Lin'Sca-1+CD49fhi cells isolated from the basal fraction of murine prostate produced luminal-like disease characteristics of human PC after transplan tation [58]. Recently, Norman J. Maitland and colleagues reported that selected cells with basal phenotypes are tumor initiating and basal SCs are the source of a luminal progeny [23]. In addition, a small population of TRA-1-60+ CD151+ CD166+ tumor initiating cells (TICs) isolated from human prostate xenograft tumors exhibited stem-like cell characteristics and recapitulated the cellular hierarchy of the original tumor in serial xenotransplanta-tion experiments [59]. Moreover, these cells expressed basal cell markers and showed increased Nuclear factor-KB (NF-kB) signaling.

4.1.2. Luminal cell-of-origin

Luminal cells are believed to be the cells of origin for human PC, because the disease is characterized by AR+ luminal cell expansion. That is why pathologists diagnose PC based on the absence of basal cell markers. It is known, that rare luminal cells which express the homeo-box gene Nkx3.1 in the absence of testicular androgens (castration-resistant Nkx3.1-express-ing cells, CARNs) are bipotential with self-renewal capability in vivo [60]. Single-cell transplantation of CARNs can reconstitute prostate ducts in renal grafts. Besides, targeted deletion of PTEN in CARNs results in rapid formation of carcinoma following androgen-mediated regeneration. Hanneke Korsten and colleagues [61] showed that genetic alterations are first seen in a subset of luminal cells expressing the progenitor markers TROP2 and SCA-1, implying that the luminal cells are the cell-of-origin in this model.

The reason why the origin of PC and the cell type of origin remains a controversial issue is in part of the distinct functional assays that were employed. Furthermore, since PC is a very heterogeneous disease it is plausible that different PCs are derived from different originating cell types.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment