Interaction of epithelial cells with the extracellular matrix is mediated through integrin receptors, which transmit signals regulating cell growth, differentiation and death. Occupation of these receptors, via Arg-Gly-Asp (RGD) recognition sequences, leads to activation of focal adhesion kinase (FAK). We treated human breast cancer cell lines with RGD-containing peptides, which can disrupt integrin attachment, and investigated alterations in FAK phosphorylation, cell detachment and death. Cells grown in vitro were treated with insulin-like growth factor-binding protein-1 (IGFBP-1) and a small, synthetic RGD-containing peptide (Gly-Arg-Gly-Asp-Thr-Pro) and its negative control peptide RGE (Arg-Gly-Glu-Ser) for either 30 min followed by immunoprecipitation of cell lysates with anti-phosphotyrosine and Western immunoblotting with anti-FAK or for 24 h followed by cell counting, immunocytochemistry and flow cytometry. Both IGFBP-1 (0-800 ng/ml) and the synthetic RGD-containing peptide (1-100 microg/ml) caused significant dephosphorylation of FAK. Furthermore, after 24 h both peptides caused detachment from the matrix and the induction of apoptosis. We conclude from these data that IGFBP-1 can interact with integrin receptors to induce FAK dephosphorylation and subsequently influence attachment and cell death.

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