Overexpression of CXCL10 in human prostate LNCaP cells activates its receptor (CXCR3) expression and inhibits cell proliferation

Chronic or recurrent inflammation plays a role in the development of many types of cancer including prostate cancer. CXCL10 (interferon-gamma inducible protein-10, IP-10) is a small secretory protein of 8.7 kDa. Recently, it has been shown that normal prostate epithelial (PZ-HPV-7) cells produce lower amounts of angiogenic CXC chemokines (GRO-alpha, IL-8) and higher amounts of angiostatic chemokines (CXCL10, CXCL11) as compared to prostate cancer cells (CA-HPV-10 and PC-3). Accordingly, we studied the effects of overexpression of CXCL10 in human prostate cancer LNCaP cells. LNCaP cells were transiently transfected with CXCL10 cDNA in pIRES2-EGFP vector. CXCL10, CXCR3, PSA and G3PDH mRNA levels were determined by semi-quantitative conventional and quantitative real-time RT-PCR and fluorescence-activated cell sorting (FACS). The expression of CXCL10 was markedly enhanced in the transfected cells at mRNA and protein levels in the cells. Overexpression of CXCL10 inhibited cell proliferation of the transfected cells by 30%-40% in serum-limited medium (1% FCS in RPMI1640 medium) and decreased PSA production. CXCR3 expression was significantly induced by the overexpression of CXCL10 as determined by RT-PCR and FACS. These results indicated that CXCL10 inhibited LNCaP cell proliferation and decreased PSA production by up-regulation of CXCR3 receptor. CXCL10 may be potentially useful in the treatment of prostate cancer.