Role of Fibroblast-Derived MT1-MMP in Oral Cancer

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Oral cavity squamous cell carcinoma (OCSCC), like many epithelial tumors, is composed of not only carcinoma cells but supporting stroma containing extracellular matrix, fibroblasts, inflammatory cells, and endothelial cells. Broadly, our lab seeks to understand mechanisms by which tumor-associated fibroblasts promote tumor proliferation and metastasis. Tumor invasion is in part mediated by the elaboration of proteinases in the tumor microenvironment that cleave surrounding extracellular matrix, chemokines, and other growth promoting molecules. The role for tumor-associated fibroblasts in tumor proliferation was recently suggested by localization of matrix metalloproteases (MMPs) primarily to surrounding fibroblasts in breast and OCSCC tumors, rather than the tumor cells. Membrane type-1 MMP (MT1-MMP) has been implicated in promoting tumor cell invasion by direct extracellular matrix degradation, activation of other MMPs, and altering tumor cell adhesion. Although identified in tumor-associated fibroblasts in OCSCC, the functional role of fibroblast-derived MT1-MMP in vivo has not been determined. We hypothesize that fibroblast-derived MT1-MMP promotes a tumor microenvironment permissive to tumor cell invasion and metastasis. To test this hypothesis we propose to assess the potential of fibroblasts to promote in vitro and in vivo OCSCC tumor cell line invasion during co-culture with 1) MT1-MMP deficient and wild-type murine fibroblasts, or 2) MT1-MMP vector or control vector transfected fibroblasts.