Binding of alpha5 monoclonal antibody to cell surface alpha5beta1 integrin modulates MMP-2 and MMP-7 activity in B16F10 melanoma cells.
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. Matrixmetallo-proteinases (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 alpha5beta1 integrin (fibronectin receptor) and MMPs (MMP-2 and MMP-7).


RESULTS
The zymographic analysis showed that ligation of cell surface alpha5beta1 integrin by alpha5 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 alpha5 monoclonal antibody, indicating the transduction of signal via FAK. The immunocytochemical study demonstrated that alpha5beta1 integrin stimulation causes rearrangement of actin fibers and its accumulation in focal adhesion sites.


CONCLUSIONS
alpha5beta1 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.
Mitra
Aparna
A
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute Kolkata, India.
Chakrabarti
Jayati
J
Chatterjee
Amitava
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D039482:Integrin alpha5 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D039482:Integrin alpha5; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2