Primary versus castration-resistant prostate cancer: modeling through novel murine prostate cancer cell lines

Abstract

Cell lines representing the progression of prostate cancer (PC) from an androgen-dependent to an androgen-independent state are scarce. In this study, we used previously characterized prostate luminal epithelial cell line (Plum), under androgen influence, to establish cellular models of PC progression. Cells derived from orthotopic tumors have been isolated to develop an androgen-dependent (PLum-AD) versus an androgen-independent (PLum-AI) model. Upon immunofluorescent, qRT-PCR and Western blot analyses, PLum-AD cells mostly expressed prostate epithelial markers while PLum-AI cells expressed mesenchymal cell markers. Interestingly, both cell lines maintained a population of stem/progenitor cells. Furthermore, our data suggest that both cell lines are tumorigenic; PLum-AD resulted in an adenocarcinoma whereas PLum-AI resulted in a sarcomatoid carcinoma when transplanted subcutaneously in NOD-SCID mice. Finally, gene expression profiles showed enrichment in functions involved in cell migration, apoptosis, as well as neoplasm invasiveness and metastasis in PLum-AI cells. In conclusion, these data suggest that the newly isolated cell lines represent a new in vitro model of androgen-dependent and –independent PC.

The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem‐like cells

“…Therefore, recent efforts are being directed towards targeting CSCs . We evaluated the ability of ST1926 to target this sub‐population of stem/progenitor cells, in DU145 and PC3 cells, using a 3D sphere formation assay . Interestingly, a recent study elucidated the role of retinoic acid, one of the products of ALDH isozymes, and other vitamin A derivatives such as ATRA, in suppressing ALDH activity among CSCs .…”

“…DU145 and PC3 PCa cell lines (ATCC) were cultured and maintained in RPMI‐1640 AQ medium (Sigma‐Aldrich) supplemented with 10% heat‐inactivated fetal bovine serum (FBS; Sigma‐Aldrich), 1% penicillin/streptomycin (Sigma‐Aldrich), and 5 µg/mL Plasmocin Prophylactic (InvivoGen). Mouse PLum‐AD (androgen‐dependent) and PLum‐AI (androgen‐independent) PCa cells, that were established in our laboratory, were cultured in PrEGM medium (Lonza) with supplements . Cells were incubated at 37°C in a humidified incubator containing 5% CO 2 .…”

“…Most PCa tumors are relatively slow growing, whereas about 10% progress rapidly from androgen‐dependent state to androgen‐independent aggressive castration‐resistant PCa (CRPC) . CRPC cells become refractory to androgen‐deprivation therapy, which results in patients' mortality . Treatment options for PCa vary between hormonal therapy and surgical interventions in clinically organ‐confined tumor, and radiation therapy or chemotherapy in progressive disease .…”

“…Treatment options for PCa vary between hormonal therapy and surgical interventions in clinically organ‐confined tumor, and radiation therapy or chemotherapy in progressive disease . To date, with all the new therapies that are being implemented to alleviate the symptoms of patients and prolong their lives, there are still no curative treatments for CRPC . It is, therefore, crucial to develop novel effective therapies for this aggressive cancer.…”

“…[14][15][16][17][18][19][20] Orally administered ST1926, has potent antitumor effects on both solid tumors and hematological malignancies. [14][15][16][17][18]21,22 We investigated ST1926 mode of action in PCa in vitro and in vivo models and assessed its effect in targeting an enriched population of PLum-AI (androgen-independent) PCa cells, that were established in our laboratory, 4 were cultured in PrEGM medium (Lonza) with supplements. 4 Cells were incubated at 37°C in a humidified incubator containing 5% CO 2 .…”