Bimolecular Interaction of Insulin-Like Growth Factor (IGF) Binding Protein-2 with αvβ3 Negatively Modulates IGF-I-Mediated Migration and Tumor Growth

Joseph Justino Pereira, T Meyer, S E Docherty, Hugh Harrington Reid, John Marshall, Erik W Thompson, Jamie Rossjohn, John T Price

Research output: Contribution to journalArticleResearchpeer-review

79 Citations (Scopus)

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 αvβ3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and αvβ3 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-7β3, which overexpressed the αvβ3 integrin. Collectively, these results indicate that αvβ3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.

Original languageEnglish
Pages (from-to)977-984
Number of pages8
JournalCancer Research
Volume64
Issue number3
DOIs
Publication statusPublished - 1 Feb 2004

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