Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
Very good read here. I've had trouble citing a direct quotation with non association of PSA and androgen independent cell lines. Here is a direct quote regarding lack of PSA expression with androgen independent cell lines.-----Cell lines targeted by Cabozantinib.
"Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa."
Very interesting. So the cross talk we see between the c-Met and AR pathways might be caused by different cells with different sets of characteristics taking over when one path way is suppressed instead of one type of cell changing receptor pathways as the cancer progresses.
In any-case, it throws some fuel on the fire for the Abiraterone / Enzalutamide + Cabo trial.
"So the cross talk we see between the c-Met and AR pathways might be caused by different cells with different sets of characteristics taking over when one path way is suppressed instead of one type of cell changing receptor pathways as the cancer progresses."
To survive cell death through androgen deprivation these cells need to seek out alternative sources to fuel growth. To compensate, these cells seek host cell interactions that don't depend exclusively on androgen . (hence mixed androgen and androgen independent cell lines) I imagine through host cell interactions, these cells can change and take on characteristics of host cell. This leads to the cancer cell's ability to rely on sources that are not exclusive to androgen. More of an adaptation to survive imo.
This notation regarding interaction of c-KIT & CD-44 has been suggested before (by prior study), but confirmation of non-PSA expression was lacking (as I best recall). I wonder why they didn't show that data? Interesting find, Hbomb.
"Though p63 tends to be underexpressed in adenocarcinomas , some cultured prostate carcinoma cell lines have been shown to express nuclear p63 . Additionally, cytoplasmic p63 has been associated with prostate cancer mortality . Cultured PrCa/CCC cells also expressed the prostate differentiation (luminal cell) marker CK8/18 (Fig. S1B), and c-kit (Fig. S1C), which co-localized with CD44. Cultured PrCa cells expressed neither chromogranin A nor PSA. The surprising lack of PSA expression was confirmed using 8 different PSA-specific antibodies on 22 different PrCa cell cultures (data not shown)."
CD44 is prostate cancer stem cell surface marker, CK8/18 express in differentiated malignant cells, so as PSA. Now it makes sense that Cabo on mCRPC with bone mets may have little effect on serum PSA even though bone scan demonstrates improvement.