Abstract
Endothelial cell-specific molecule-1 (ESM-1), also known as endocan, is a soluble proteoglycan expressed by the vascular endothelium, which also circulates in the bloodstream. Inflammatory cytokines and proangiogenic growth factors increase its expression, and increased serum levels have been reported in several cancer types and immunocompetent patients with sepsis. The aim of this study was to analyze the expression profile of CXC-chemokines and the effects of ESM-1 gene knockdown in proliferation, migration and CXC-chemokine expression in highly metastatic human prostate PC-3 cells. Expression profiles of CXC-chemokines were analyzed in metastatic PC-3 and non-tumorigenic PWR-1E cells. siRNA-mediated knockdown of ESM-1 was performed into PC-3 cells, which were subsequently tested for cell migration and proliferation. Effect of siRNA transfection on CXC-chemokine expression was further quantified at the transcript and protein level. RT-qPCR analysis and sandwich ELISA assay revealed higher levels of ESM-1 and several CXC-chemokines in metastatic PC-3 cells compared to non-tumorigenic PWR-1E. Transfection of PC-3 cells with ESM-1-siRNA decreased cell migration with no effect on proliferation, and it was accompanied by decrease in the transcript and protein levels of the angiogenic chemokine CXCL3. We report here for the first time the ESM-1 targeting in PC-3 cells, which resulted in decreased migration, which may be related, at least in part, to decreased expression of the angiogenic CXCL3 chemokine, whose expression was found to be reduced in ESM-1-siRNA transfected cells. Additional studies are required to ascertain the biological role of ESM-1 in prostate cancer cells and the link with the expression of CXCL3.