Study On The Implication Of Matrix Metalloproteinase-2 (MMP-2) During The Adhesion And Migration Of Human Melanoma Cell A375

Malignant melanomas are notorious for their tendency to metastasize. Gelatinases, also known as the matrix metalloproteinases(MMP)-2 and -9, have been long recognized related to the malignancy of melanoma as major contributors to the essential steps in melanoma progression, the degradation of basement membranes and remodeling of the extracellular maxtrix(ECM). Besides, gelatinases have also been identified as important proteolytic executors and regulators in various physiological and pathological states including angiogenesis, tumor invasion and migration. According to recent researches, the gelatinases are not only expressed in tumor cells but also in stromal cells, and they have been shown to interact with a broad range of non-matrixproteins including integrins besides proteins in ECM. In migrating melanoma, Integrinαvβ3 is the main transmembrane receptor that binds to RGD–containing ligands to provide dynamic interactions between extracellular ligands and actin cytoskeleton and signalling machineries. However, the recognition between MMP-2 and integrinαvβ3 is not the RGD but the PEX sequence of MMP-2 , but no data are available on the possible role of MMP-2 in signalling through its interaction withαvβ3.In our study, we found constitutive expression of both MMP-2 and MMP-9 in human melanoma A375 by gel zymography. Using an in vitro model of 2-D migration and broad spectrum MMP inhibitor, we demonstrated that MMP-2, but not MMP-9, is a key enzyme for A375 cells spreading and migration. Results of observing the distribution of MMP-2 and F-actin during A375 cells spreading indicated a connection between the proteinase and actin cytoskeleton. In support of these data, MMP-2 andαvβ3 were specifically colocalized at the leading edge of A375 cells. Finally, we found that both MMP-2 and MMP-9 can affect the ligand-binding ofαvβ3 by adhesion systems. Altogether, these data provide the evidence for the implication of MMP-2 in human melanoma motility, probably through the interaction of MMP-2 with integrinαvβ3 that act as a linker of many signaling pathways.