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Demonstration that a Human Hepatoma Cell Line Produces a Specific Insulin-Like Growth Factor Carrier Protein^*

Charles A. Dana Research Institute and the Haruard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215; and the Wistar Institute (B.B.K., D.P.A.), Philadelphia, Pennsylvania 19104

Address requests for reprints to: Alan C. Moses, M.D., Department of Medicine, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215.

Insulin-like growth factors (IGF's) circulate in blood complexed to specific carrier proteins. The BRL 3A and BRL 3A2 rat liver cell lines secrete a 30,000–50,000 mol wt IGF carrier protein. Since the liver parenchymal cell is a likely source of IGF carrier protein synthesis, we have evaluated medium conditioned by three human hepatocellular carcinoma- or hepatoblastoma-derived cell lines for the presence of IGF carrier protein. The HEP G2 and the HEP 3B, but not the PLC/PRF/5, cell lines secrete a specific IGF carrier protein(s) into serumfree medium. This carrier protein is specific for IGF molecules. Multiplication-stimulating activity, IGF I, and IGF II were equipotent in competing for the binding of [¹²⁵I]multiplication-stimulating activity to HEP G2 medium. The HEP G2 IGF carrier protein is trypsin sensitive, acid stabile, and does not contain a glycoprotein moiety. It has a molecular size of 30,000–50,000, as assessed by Sephadex G-200 gel filtration. These studies suggest that the HEP G2 cell line is a useful model to study the synthesis and secretion of human IGF carrier protein. (J Clin Endocrinol Metab 56: 1003, 1983)

^* This work was supported in part by Grant RR-01032 from the General Clinical Research Centers Program of the Division of Research Resources, NIH. Work performed at the Wistar Institute was supported by American Cancer Society Grants IN-215 and IN-413; NIH Research Grants CA-18470, CA-10815, and CA-25875; and NIH Career Development Award CA-00510.

Received August 2, 1982.

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