Binding of a5 Monoclonal Antibody to Cell Surface a5b1 Integrin Modulates MMP-2 and MMP-7 Activity in B16F10 Me

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Abstract
The integrin multigene family, comprising at least 21 distinct heterodimeric complexes, includes receptors for all major extracellular proteins such as fibronectin, laminin, vitronectin, and collagens. These receptors play important roles in various physiological processes. Matrixmetalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade the extracellular matrix (ECM) components in physiological conditions. MMPs can degrade all structural components of the ECM, which is one of the critical aspects of tumor cell invasion. The role of matrilysin (MMP-7) in the progression of various carcinomas was recently addressed. Evidence of interplay between integrin function and ECM matrix integrity has come from experiments showing that integrin-ECM contacts can regulate expression and function of MMPs. In this communication, we report on an interesting interrelationship between cell surface a5b1 integrin (fibronectin receptor) and MMPs (MMP-2 and MMP-7). Results: The zymographic analysis showed that ligation of cell surface a5b1integrin by a5 monoclonal antibody leads to the expression and activation of MMP-2 and MMP-7 in B16F10 melanoma cells. The immunoblot confirmed the tyrosine phosphorylation of FAK in B16F10 cells grown in presence of a5 monoclonal antibody, indicating the transduction of signal via FAK. The immunocytochemical study demonstrated that a5b1 integrin stimulation causes rearrangement of actin fibers and its accumulation in focal adhesion sites. Conclusion: a5b1 integrin-induced expression and activation of MMP-2 and -7 indicates the role of tumor cell surface integrin receptor in the modulation of MMPs and, thereby, the invasive property of tumor cells.

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