Autocrine tumor growth regulation and tumor-associated hypoglycemia in murine melanoma B16 in vivo

Abstract

A substance immunochemically cross-reactive with insulin (SICRI) appears in melanoma B16 growing in diabetic and nondiabetic C57BL/6 mice. Progression of tumor size is paralleled by the increase of SICRI levels in the serum of both diabetic and nondiabetic animals; this increase correlates with a decreased concentration of circulating glucose and an elevated concentration of growth hormone in blood. Melanoma B16 grown under serum-free culture conditions secretes SICRI into the medium. Affinity-purified SICRI stimulates glucose uptake by rat epididymal adipocytes and competes with radiolabeled insulin for binding to these cells. Low concentrations of SICRI enhance growth of cultured melanoma B16 cells, whereas high concentrations of this substance have inhibitory growth effects on these cells. Porcine insulin, human insulin-like growth factors I and II, human growth hormone, platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor have negligible influence on growth of melanoma B16.