Examination of the Unique Role of Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) in Prostate Cancer Invasion and Metastasis

Abstract

Abstract : This grant was initiated on January 1 2002 with the goal of studying the role of membrane type 1 matrix metalloproteinase (MT1-MMP) in prostate cancer invasion and metastasis. The basic concept of this grant is that the membrane enzyme MT1-MMP plays a central role in prostate cancer metastasis. Although considerable progress has been made in the last decade in our understanding the pathophysiology of cancer invasion and metastasis, the pathobiology of prostate cancer is not well understood. Increasing evidence demonstrated that the ability of prostate cancer cells to migrate across basement membranes and to degrade extracellular matrix (ECM) relies on the activity of matrix metalloproteinases (MMPs). MT1-MMP is considered to be the most important proteinase involved in cancer cell migration, invasion and metastasis. The rational for this grant is based on the fact that production and activation of MMPs, especially proMMP-2 (pMMP-2), in prostate cancer is required for cancer cell invasion and metastasis. Cell motility is a critical determinant of prostate cancer metastasis. MT-MMPs are responsible for cell surface activation of pMMP-2, thereby representing a key factor in cancer progression. Regulation of MT-MMP function, particularly in cancer cell migration, a key step for metastasis is poorly understood; elucidation of this mechanism is important for anti-metastatic drug development. Therefore, the goal of this proposal is to elucidate the role of MT1-MMP in human prostate cancer cell motility, invasiveness, and metastasis and to develop reagents for reducing prostate cancer metastasis.