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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/24203
Title: The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells
Authors: Kulrut Borrirukwanit
Marc A. Lafleur
Francesca A. Mercuri
Tony Blick
John T. Price
Rafael Fridman
Joseph J. Pereira
Vijittra Leardkamonkarn
Erik W. Thompson
University of Melbourne
Mahidol University
St Vincent's Institute
Wayne State University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-May-2007
Citation: Matrix Biology. Vol.26, No.4 (2007), 291-305
Abstract: The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth. © 2006.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=34247538440&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/24203
ISSN: 0945053X
Appears in Collections:Scopus 2006-2010

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