Abstract
BackgroundMatrix metalloproteinase-2 (MMP-2) is a key regulator in the migration of tumor cells. αvβ3 integrin has been reported to play a critical role in cell adhesion and regulate the migration of tumor cells by promoting MMP-2 activation. However, little is known about the effects of MMP-2 on αvβ3 integrin activity and αvβ3 integrin-mediated adhesion and migration of tumor cells.Methodology/Principal FindingsHuman melanoma cells were seeded using an agarose drop model and/or subjected to in vitro analysis using immunofluorescence, adhesion, migration and invasion assays to investigate the relationship between active MMP-2 and αvβ3 integrin during the adhesion and migration of the tumor cells. We found that MMP-2 was localized at the leading edge of spreading cells before αvβ3 integrin. αvβ3 integrin-mediated adhesion and migration of the tumor cells were inhibited by a MMP-2 inhibitor. MMP-2 cleaved fibronectin into small fragments, which promoted the adhesion and migration of the tumor cells.Conclusion/SignificanceMMP-2 cleaves fibronectin into small fragments to enhance the adhesion and migration of human melanoma cells mediated by αvβ3 integrin. These results indicate that MMP-2 may guide the direction of the tumor cell migration.
Highlights
Tumor metastasis characterized by the dissemination of tumor cells from a primary site to the distant sites is the most frequent cause of death for cancer patients [1,2]
To study the relationship of Matrix metalloproteinase-2 (MMP-2) and avb3 integrin in tumor cell adhesion and migration, human A375 melanoma cells were suspended or seeded onto coverslips coated with human fibronectin
E, approximately more than 59% tumor cells adhered to the culture wells coated with aminophenylmercuric acetate (APMA)-activated matrix metalloproteinases (MMPs)-2 compared with those cells blocked with RGD peptides. These results demonstrated that MMP-2 and avb3 integrin were expressed on A375 cells, and they might interact with each other
Summary
Tumor metastasis characterized by the dissemination of tumor cells from a primary site to the distant sites is the most frequent cause of death for cancer patients [1,2]. The initial step of tumor metastasis is a process of invasive tumor cell migrating in basement membrane, which implicates cell adhesion and migration as well as proteolysis of the extracellular matrix (ECM). This step involves many molecules including matrix metalloproteinases (MMPs) and integrins [3,4,5,6,7,8,9,10,11,12,13,14,15,16]. Avb integrin has been reported to play a critical role in cell adhesion and regulate the migration of tumor cells by promoting MMP-2 activation. Little is known about the effects of MMP-2 on avb integrin activity and avb integrin-mediated adhesion and migration of tumor cells
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