B7-H1 enhances proliferation ability of gastric cancer stem-like cells as a receptor

Abstract

Cancer stem-like cells (CSCs) are a rare tumorigenic population with the ability to self-renew in numerous cancer types. Their existence is considered a pivotal contributor to tumor recurrence. B7-H1 is a ligand of inhibitory inducible co-stimulator (ICOS) that is broadly expressed on various human cancers. ICOS acts as a ligand of programmed death-1 (PD-1) on T cells, induces the immune escape of cancer cells and also acts as a receptor mediating anti-apoptotic effects on cancer cells. However, the expression and function of B7-H1 on CSCs is not yet clear. In the present study, gastric cancer samples were collected and the B7-H1 expression in gastric cancer CSCs was detected. Ki67, a proliferation marker, was found to be expressed at a higher rate in B7-H1+ CSCs compared with the B7-H1-counterparts. SGC-7901 cells, a gastric cancer cell line, were cultured in serum-free medium to form sphere cells that possessed stem cell characteristics and could express B7-H1 with the stimulation of interferon-γ. The proliferative ability of sphere cells was enhanced following B7-H1 activation with recombinant PD-1 in vivo and in vitro. This effect could be eliminated by neutralizing B7-H1. Overall, B7-H1 can act as a stimulating receptor for CSCs, and induce CSC proliferation. Blocking B7-H1 on CSCs may possess therapeutic potential for treating gastric cancer.