C4-2 Cells

The C4-2 cell line is an androgen-independent human prostate cancer model derived from the parental LNCaP cell line. It was established through a stepwise in vivo selection process involving co-injection of LNCaP cells with human bone stromal cells (MS cells) into castrated immunodeficient mice, leading to the emergence of androgen-insensitive tumors. The C4-2 subline was specifically derived from the C4 variant after further passage in castrated hosts, and it retains the ability to grow and form tumors in androgen-depleted conditions without the need for stromal support.

C4-2 cells maintain the prostate-specific antigen (PSA) production and expression of the androgen receptor (AR), including the characteristic T877A AR point mutation inherited from LNCaP, but display reduced androgen responsiveness compared to the parental line. While LNCaP cells require androgens for growth, C4-2 cells proliferate in androgen-depleted environments and continue to express PSA and AR-regulated genes, making them a robust model for castration-resistant prostate cancer (CRPC). In vitro, C4-2 cells grow more rapidly than LNCaP under standard culture conditions, and they also exhibit improved tumorigenicity in vivo. When injected subcutaneously into immunocompromised mice, C4-2 cells readily form tumors, a feature that contrasts with the slower or less consistent tumorigenic potential of LNCaP cells.

The C4-2 model has been widely used to study mechanisms of resistance to androgen deprivation therapy (ADT), the role of intracrine androgen metabolism, and the molecular pathways underpinning CRPC progression. It retains expression of prostate-specific membrane antigen (PSMA), although at lower levels than LNCaP, and displays unique responses to androgen stimulation and antiandrogen therapies. These attributes make C4-2 a cornerstone model for evaluating new therapeutics targeting advanced prostate cancer.