Panoply™ Human PSCA Over-expressing Stable Cell Line

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. PSCA is involved in the proliferation and invasion of prostate cancer cells, but the underlying mechanisms remain unclear. Here, researchers aimed to investigate the regulatory role of PSCA gene expression in interleukin-6 (IL-6) autocrine secretion in prostate cancer cells. Results showed that stable knockdown of the PSCA gene delayed prostate cancer cell proliferation, migration, and invasion, while overexpression of the PSCA gene enhanced prostate cancer cell proliferation, migration, and invasion in vitro and promoted lung metastasis in vivo. Importantly, PSCA gene expression was involved in IL-6 secretion and positively regulated the p38/NF-κB/IL-6 signaling pathway, thereby enhancing prostate cancer cell invasion and metastasis. Both PSCA and IL-6 expression were significantly associated with poor biochemical recurrence-free survival in prostate cancer cells. Kaplan-Meier analysis demonstrated that PSCA protein expression had prognostic value for overall survival. These results indicate that PSCA regulates the expression and secretion of IL-6 in human prostate cancer cells through the p38/NF-κB signaling pathway and that PSCA may serve as a potential diagnostic marker and therapeutic target for PSCA-positive prostate cancer.

To investigate whether p38 and NF-κB activation are causally involved in PSCA-mediated IL-6 secretion, the researchers tested the effects of drugs that inhibit p38 and NF-κB activation. As shown in Figures 1A, 1D, and 1E, SB202191 treatment inhibited p38 MAPK activation in PSCA-overexpressing cells. Furthermore, the researchers observed a significant decrease in NF-κB and IL-6 expression. Because this result suggests that p38 is a major mediator of IL-6 secretion, they transfected PSCA-overexpressing cells with specific siRNAs to block the p38-α (MAPK14) and p38-β (MAPK11) isoforms, confirming the involvement of p38 in regulating IL-6 secretion. Transfection with p38α- and p38β-siRNAs completely blocked PSCA-stimulated total p38 phosphorylation compared to nonspecific oligonucleotide controls (Figures 1B and 1C). Similarly, the researchers evaluated the effects of NF-κB inhibition on PSCA-induced IL-6 expression. Pretreatment with QNZ significantly reduced IL-6 expression. However, the NF-κB inhibitor QNZ had no effect on PSCA and p38 mRNA and protein.

Figure 1. Inhibition of p38 MAPK effectively blocks PSCA mediated IL-6 mRNA and protein levels. (Liu L, et al., 2017)