Vo1.153, No. 3,1988 June 30,1988 BIOCHEMICALAND BIOPHYSICALRESEARCHCOMMUNICATIONS Pages 1076-1083 INSULIN-LIKE GROWTH FACTORS STIMULATE CHEMOTAXIS IN HUMAN MELANOMA CELLS 1 Mary L. Stracke , Ellse C. Kohn*, Sadie A. Aznavoorlan, Lori L. Wilson, David Salomon**, Henry C. Krutzsch, Lance A. Liotta, and Elliott Schiffmann Laboratory of Pathology, *Medicine Branch, and **Laboratory of Tumor Immunology and Biology National Cancer Institute National Institutes of Health Bethesda, Maryland 20892 Received May ii, 1988 Summary: Insulin and insulin-llke growth factors stimulate motility in the hlghly metastatic human melanoma cell llne, A2058. Insulln-like growth factor-I (IGF-I) is the most potent with a maximal response at a concentration of i0 nMeompared to the activities of insulin and Insulin-llke growth factor-ll (IGF-II) which peak at 300-400 nM. Using checkerboard analysis, the responses to IGF-I and insulin are predominantly chemotactlc, although insulin had a significant chemokinetlc component. Pertussis toxin does not inhibit the response to any of these polypeptldes. However, in previous studies, it was shown that the motile response to autocrine motility factor from these same A2058 cells was markedly inhibited by pertussis toxin. 1251-labelled IGF-I binds saturably and speclfically to the A2058 cells. Scatchard analysis indicates a high binding affinity (Kd-~ 3 x 10-10M) and an estimated 5000 receptors/cell. These studies indicate that in addition to their mltogenic properties, certain growth factors may profoundly enhance metastasis of tumor cells by their ability to induce motility. © 1988~ademic Press, Inc. While uncontrolled replication is characteristic of malignant Cells, it is also clear that locomotion and its regulation are crucial for their metastasis. A number of agents have been shown to stimulate tumor cell motility (i-4). Of the growth factors known to stimulate mitogenesls in tumor cells, only bombesln has been found to induce motility (5). In the course of isolating an autoerine motility factor for human melanoma cells 1To whom correspondence should be sent. Abbreviations: AgF: autocrine motility factor; 0.1Z BSA-DMEH: Dulbecco's Modified Eagle's Medium with 1 mg/ml of bovine serum albumin; IGF-I: insulln-like growth factor-I; IGT-II: insulln-llke growth factor-IS; PT: pertussls toxin; EGF: epidermal growth factor; PDGF: platelet-derlved growth factor; ECGF: endothelial cell growth factor; FGF: flbroblast growth factor 0006-291X/88 $1.50 Copyright © 1988 by Academic Press, Inc. All rights of reproduction in any form reserved. 1076