Hepatocyte growth factor expression correlates with cyclooxygenase-2 pathway in human salivary gland tumors

Abstract

It has been reported that cyclooxygenase-2 (COX-2) plays roles in cell proliferation, tumor invasion and inhibition of apoptosis. We reported COX-2 expression in salivary adenoma and its involvement in inhibition of apoptosis. COX-2 is known to induce a number of cytokines and growth factors. On the other hand, hepatocyte growth factor (HGF) plays roles such as cell migration, proliferation, angiogenesis and inhibition of apoptosis. Recently it has been reported that HGF also plays a role in tumor differentiation in salivary gland tumors. So, we investigated that whether COX-2 expression affected HGF expression clinicopathologically, and discussed the roles of COX-2 pathway in salivary gland tumors. Tissues samples were pleomorphic adenomas (n = 40) obtained surgically. COX-2 expression and HGF expression were examined immunohistochemically. Immunostaining intensities of COX-2 and HGF were classified as +3 to 0. Spearman's rank correlation was used to examine correlation of COX-2 and HGF expression. Furthermore, a salivary gland tumor cell line, HSG, was cultured after administration of either 0, 10, 100 units of COX-2 and quantification of HGF mRNA was analyzed by Real Time PCR using the Light Cycler System. In pleomorphic adenoma, COX-2 and HGF were mainly expressed in luminal tumor cells, and the sites of expression of the two were almost the same. Immunostaining intensity of COX-2 expression was significantly correlated with intensity of HGF expression (p = 0.003, r = 0.457). Moreover, the content of HGF mRNA expression increased when COX-2 was administered to salivary gland tumor cell line HSG. It is suggested that COX-2 expression may induce HGF expression in salivary gland tumors.