Abstract
Both the integrin and insulin-like growth factor binding protein (IGFBP) families independently play important roles in modulating tumor cell growth and progression. We present evidence for a specific cell surface localization and a bimolecular interaction between the alpha v beta 3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and alpha v beta 3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was observed in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7 beta 3, which overexpressed the alpha v beta 3 integrin. Collectively, these results indicate that alpha v beta 3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology*
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Cell Division / drug effects
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Cell Division / physiology
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / physiology*
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Humans
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Insulin-Like Growth Factor Binding Protein 2 / metabolism*
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Insulin-Like Growth Factor I / antagonists & inhibitors*
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Insulin-Like Growth Factor I / physiology
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Insulin-Like Growth Factor II / antagonists & inhibitors
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Insulin-Like Growth Factor II / physiology
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Integrin alphaVbeta3 / biosynthesis
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Integrin alphaVbeta3 / immunology
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Integrin alphaVbeta3 / metabolism*
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Vitronectin / pharmacology
Substances
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Antibodies, Monoclonal
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Insulin-Like Growth Factor Binding Protein 2
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Integrin alphaVbeta3
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Vitronectin
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Insulin-Like Growth Factor I
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Insulin-Like Growth Factor II