Anti-alpha3 integrin antibody induces the activated form of matrix metalloprotease-2 (MMP-2) with concomitant stimulation of invasion through matrigel by human rhabdomyosarcoma cells.
Proteolytic enzymes, such as matrix metalloproteases (MMPs), play a pivotal role in cancer invasion and metastasis. Invasive human rhabdomyosarcoma cells (RD) secreted proMMP-2 (72-kDa progelatinase). We found that anti-alpha3 and -alpha2 integrin antibodies induced the activated form of MMP-2 and enhanced proMMP-2 secretion by RD cells. The effect of anti-alpha2 integrin antibody was less prominent than that seen with anti-alpha3 integrin antibody. Moreover, we have found that anti-alpha3 and -alpha2 integrin antibodies enhanced RD-cell invasion through matrigel (reconstituted basement membrane) by 2.6- and 2.0-fold respectively this process was abrogated by neutralizing antibody to MMP-2. These data suggest that signaling events induced by anti-alpha3 integrin antibody may be involved in RD-cell invasion as a result of modulation of matrix-metalloprotease expression.
Kubota
S
S
Department of Physiological Chemistry and Nutrition, Faculty of Medicine, The University of Tokyo, Japan. kubota@eiyo.m.u-tokyo.ac.jp
Ito
H
H
Ishibashi
Y
Y
Seyama
Y
Y
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D003094:Collagen; D004338:Drug Combinations; D004790:Enzyme Induction; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D039422:Integrin alpha3; D016023:Integrins / Q000276:immunology* / Q000378:metabolism; D007797:Laminin; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000378:metabolism / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D039422:Integrin alpha3; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2