Matrix metalloproteinases in tumor invasion: role for cell migration.

Matrix metalloproteinases (MMP) play a role in a wide range of tumorigenesis, including early carcinogenesis events, tumor growth and tumor invasion and metastasis. Given that the ability of tumor cells to infiltrate and disseminate widely is what makes the tumors malignant, a role of MMP in cell migration during this invasive and metastatic process is important. There are two types of cancer cell migration: single cell locomotion and cohort migration (cell movement en mass keeping cell-cell contact, which is frequently seen in better differentiated carcinomas). Cell surface localization and activation of MMP is essential for cells to migrate, through rearrangement of extracellular matrix (ECM) to suit cell migration. Certain MMP, such as gelatinases and membrane -type 1 MMP, have special mechanisms to localize at leading edges in both types of cell migration. Moreover, in cohort migration, expression of these MMP is regulated via cell-cell contact within migrating cell sheets and confined to the foremost pathfinder cells of the migrating cell sheets. New roles of cell surface MMP, such as cleavage of cell surface receptors or cofactors involved in cell-ECM interactions during cell migration, are also discussed.