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vß3 Negatively Modulates IGF-I-Mediated Migration and Tumor Growth1
1 Breast-Bone Metastasis/Cell Migration Laboratory and 2 VBCRC Laboratory, St. Vincent’s Institute of Medical Research, Fitzroy, and 3 The Protein Crystallography Unit Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia, and 4 St. Thomas’ Hospital, Richard Dimbleby Department of Cancer Research, Lambeth Palace Road, London, United Kingdom
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 
vß3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and vß3 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-7ß3, which overexpressed the vß3 integrin. Collectively, these results indicate that vß3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.
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