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Growth Inhibition of Human Breast Cancer Cells in Vitro with an Antibody against the Type I Somatomedin Receptor¹

Department of Medicine, Division of Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7884

Insulin and insulin-like growth factors (IGFs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR), expressed in these cells, may mediate the mitogenic effects of these peptides. We have examined the effect of type I SR blockade on human breast cancer growth with a monoclonal antibody (-IR₃) that blocks the receptor binding domain. -IR₃ inhibited binding of ¹²⁵I-IGF-I in all breast cancer cell lines tested. Binding affinity of -IR₃ was 2 to 5 times higher than that of IGF-I in MDA-231 (K_d 2.1 nM) and MCF-7 cells (K_d 0.6 nM), respectively. In the presence of 10% calf serum, the antibody inhibited anchorage-independent growth of six of seven breast cancer cell lines. This inhibition was reversible with excess IGF-I. In serum-free medium, -IR₃ blocked IGF-I-stimulated DNA synthesis in four of four breast cancer cell lines (MCF-7, ZR75-1, MDA-231, and HS578T). However, the antibody did not inhibit basal growth of any of the breast cancer cell lines in serum-free conditions. In three estrogen receptor-positive, estrogen-responsive breast cancer cell lines (MCF-7, ZR75-1, and T47D), type I SR blockade with -IR₃ failed to block estrogen-stimulated DNA synthesis or cell proliferation, indicating that secreted IGF activity is not the sole mediator of the growth effects of estrogen. In conclusion, antibody-mediated type I SR blockade does not inhibit basal growth of breast cancer cells under serum-free conditions, arguing against a critical autocrine role of endogenously secreted IGF activity in vitro. However, type I SR blockade inhibits breast cancer cell growth in the presence of serum, suggesting that serum IGFs might be critical endocrine or paracrine regulators of human breast cancer.

¹ Supported in part by NIH Grants R01 CA 30251 and P01 30195 and by a Veterans Administration Career Development Award.

² Recipient of an Associate Investigator Career Development Award from the Veterans Administration. Present address: Division of Medical Oncology, Vanderbilt University, V. A. Medical Center, 1310 24th Avenue South, Nashville, TN 37212.

³ To whom requests for reprints should be addressed.

Received 10/13/88. Revised 6/15/89. Accepted 8/14/89.

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