Microphysiometry to evaluate real-time response of mammary epithelial cells to IGF-I

The Cytosensor(R) Microphysiometer, a biosensor developed by Molecular Devi ces, was used to assay rapid binding activity of IGF-I for bovine mammary e pithelial cell lines. Insulinlike growth factor-I (IGF-I) is a potent mitog en for mammary epithelial cells and has been implicated in breast cancer ce ll proliferation, a leading cause of cancer death of women in the U.S. toda y. IGF-I acts by binding to cell surface receptors. We are interested in ho w autocrine secretion might alter the activity and regulation of IGF-I. Real-time changes in excretion of protons, which we assert results from IGF -I binding, are detected by the Cytosensor(R) Microphysiometer and can be c orrelated with cellular activity. We present IGF-I dose-dependent: response s as well as correlated binding data to detect cell surface receptor concen tration and thymidine incorporation results to determine cell proliferation following IGF-I stimulation. We examine the effect of insulin-like binding protein-3 (IGFBP-3) both in the presence and absence of IGF-I. We believe comparison of autocrine and paracrine environments for IGF-I stimulation, a nd the components contributing to the binding of IGF-I to the cell membrane receptor may provide pertinent information for the development of interven tion schemes to slow or interrupt IGF-I binding to tumor cells and therefor e cancer growth.