Bimolecular interaction of insulin-like growth factor (IGF) binding protein-2 with αvβ3 negatively modulates IGF-I-mediated migration and tumor growth

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 alphavbeta3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and alphavbeta3 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-7beta3, which overexpressed the alphavbeta3 integrin. Collectively, these results indicate that alphavbeta3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.