Mechanism of Cancer Invasion and Metastasis by MMP

Abstract

Degradation of extracellular matrix (ECM) components by matrix metalloproteinases (MMPs) is critical for tumor cell invasion and metastasis. Disruption of the basement membrane is a crucial step for tumor progression. Of the MMPs, MMP-2 is notable because its activity degrades type IV collagen, a major component of the basement membrane. MT1-MMP has been recognized as a key factor for pro-MMP-2 activation. Recent studies have revealed that tumor cells utilize MMPs, such as MMP-2, produced by neighboring stromal cells including fibroblasts rather than by tumor cells themselves for tumor progression, invasion, and metastasis. It has also been found that tumor cells can stimulate stromal cell production of MMPs via soluble factors such as cytokines or through cell-cell interaction mediated by cell adhesion molecules such as EMMPRIN. EMMPRIN, belonging to immunoglobulin superfamily, is a transmembrane glycoprotein with two extracellular domains and a short cytoplasmic domain. Several investigators have reported that expression of EMMPRIN is enriched in a variety of human carcinomas and that it contributes to tumor invasion and metastasis by stimulating nearby fibroblasts to increase secretion of MMPs. In our study, we confirmed that EMMPRIN is highly expressed with laryngeal cancer cells and is involving the production of MMPs from fibroblasts. Further research would clarify the role of EMMPRIN in the mechanism of cancer invasion and its role in metastasis in more detail. Such additional research might demonstrate that EMMPRIN would be a new target in the treatment of cancer.