Identification and characterization of a novel CXC chemokine in xenograft tumor induced by mas‐overexpressing cells

Abstract

Overexpressions of G protein-coupled receptor (GPCR) with elevated downstream signaling events have been reported in various tumors. However, the cellular mechanism that GPCR overexpression leads to tumor formation is largely unknown. The orphan GPCR mas was originally isolated from a human epidermoid carcinoma. In vivo studies of mas-overexpressing cells suggested that xenograft tumor formation was positively correlated with the levels of mas expression. Histochemical analysis indicated that xenograft tumor consisted of mas-transfected and stromal cells. Biochemical analyses revealed that cells overexpressing mas exhibited significantly increased anchorage-independent growth, whereas there was no significant difference in cell proliferation in comparison with empty vector-transfected control cells. Expression profiling using mRNA differential display and Northern analysis indicated an elevated expression of GRO and a novel CXC chemokines, tumor-induced factor (TIF), in mas-transfected cells and xenograft tumor. Bacterially expressed recombinant TIF was found to act as a neutrophil chemoattractant in a chemotactic assay. These results suggest that mas overexpression enables anchorage-independent growth of transformed cells, and interplays of secreted chemokines with stromal cells modulate xenograft tumor formation. Importantly, a novel CXC chemokine, TIF, was identified in the xenograft tumor tissues.