Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function

Matrix metalloproteinases (MMPs) play a central role in numerous normal and pathological events. The precise regulation of production and activation of MMPs is important in determining their correct localization and the appropriate extent of their action. Because MMPs have an incredibly diverse number of substrates and because cleavage of these substrates leads to numerous cellular responses, inappropriate regulation is potentially destructive and, accordingly, MMPs have been implicated in a number of disease processes. Many physiological regulators of MMP production that have been characterized are soluble cytokines and growth factors, but the possibility that cell-surface interactions regulate MMP production and activation has also been appreciated. Emmprin (basigin, CD147) is an integral plasma membrane glycoprotein of the Ig superfamily that has the ability to induce synthesis of various MMPs. This chapter reviews the current knowledge of emmprin, especially with respect to induction of MMP production in cancer. Tumor cells create a pericellular environment in which many MMPs and other proteases become concentrated, thereby enhancing their ability to invade extracellular matrices and to process precursors of factors that promote tumor progression. Several emmprin-binding partners, including MMP-1, have been characterized but their roles in MMP induction and in tumor progression are not clear. Although recent evidence suggests that stromal production of MMPs promotes tumor progression, the relative contributions of stromal versus tumor cell production of MMPs and the role of emmprin in regulating MMP production from either source need to be elaborated. In addition to cancer, emmprin is involved in numerous physiological and pathological events that may or may not involve regulation of MMP synthesis.