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 ␣v␤3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and ␣v␤3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was

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... ved in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7␤3, which overexpressed the ␣v␤3 integrin. Collectively, these results indicate that ␣v␤3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.