Insulin-like growth factors stimulate chemotaxis in human melanoma cells

• Published in: Biochemical and biophysical research communications Vol. 153; no. 3; pp. 1076 - 1083
• Main Authors: Stracke, Mary L., Kohn, Elise C., Aznavoorian, Sadie A., Wilson, Lori L., Salomon, David, Krutzsch, Henry C., Liotta, Lance A., Schiffmann, Elliott
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 30.06.1988; Elsevier
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cell Line; Cell Movement; Chemotaxis - drug effects; Fundamental and applied biological sciences. Psychology; Humans; Insulin - pharmacology; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor II - pharmacology; Melanoma - pathology; Pertussis Toxin; Protein hormones. Growth factors. Cytokines; Proteins; Somatomedins - pharmacology; Virulence Factors, Bordetella - pharmacology; IGF-I; PT; FGF; EGF; PDGF; 0.1% BSA-DMEM; AM; ECGF; IGF-II; Pancreatic hormone; Motility; Radiolabelling; Somatomedin C; Melanoma; Islet activating protein; Chemotaxis; Insulin like growth factor 2; Insulin; Cell substratum interaction; Dose activity relation; Proteins; Protein hormone; Cell line; Tumor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(88)81338-X

Insulin and insulin-like growth factors stimulate motility in the highly metastatic human melanoma cell line, A2058. Insulin-like growth factor-I (IGF-I) is the most potent with a maximal response at a concentration of 10 nM compared to the activities of insulin and insulin-like growth factor-II (IGF-II) which peak at 300–400 nM. Using checkerboard analysis, the responses to IGF-I and insulin are predominantly chemotactic, although insulin had a significant chemokinetic component. Pertussis toxin does not inhibit the response to any of these polypeptides. 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. 125I-labelled IGF-I binds saturably and specifically to the A2058 cells. Scatchard analysis indicates a high binding affinity (Kd ∼ 3 × 10 −10 M) and an estimated 5000 receptors/cell. These studies indicate that in addition to their mitogenic properties, certain growth factors may profoundly enhance metastasis of tumor cells by their ability to induce motility.