Role of Hepatocyte Growth Factor and c-Met Receptor in Neoplastic Conditions of Salivary Glands

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Signaling via hepatocyte growth factor (HGF) and the HGF receptor, c-Met, plays important roles in human salivary glands and salivary gland tumors. Various effects of HGF, including acceleration or inhibition of cell growth, enhancement of cell motility, increase of angiogenesis, inhibition of apoptosis and induction of morphogenesis, have been demonstrated in various epithelial cells. Our recent analysis of HGF regarding saliva, salivary gland and salivary gland tumors demonstrated that: 1) HGF was basically localized in luminal cells of fetal, normal salivary glands and salivary gland tumors; 2) saliva contained HGF protein on ELISA; 3) HGF tended to be more intensely expressed in benign salivary gland tumors than in malignant salivary gland tumors; 4) HGF/c-Met signaling was associated with cell scattering and invasion into matrix in the ACC3 adenoid cystic carcinoma cell line; 5) prognosis was poor and correlated to metastasis in high-grade salivary gland carcinomas with c-Met overexpression. These profiles suggest that HGF/c-Met systems may play significant roles in differentiation or tumor progression for salivary gland tumors.