• Open Access

Insulin and Insulin-like Growth Factor 1 Stimulate Proliferation of Metastatic Variants of Colon Carcinoma 26



The proliferation rate of malignant cells in vivo is one of the important factors which affect the formation of tumor metastasis. A highly metastatic variant of mouse colon adenocarcinoma 26 (NL- 17) grew more rapidly than a low-metastatic variant (NL-44) both in vitro and in vivo. The effect of growth factors on the proliferation of NL-17 and NL-44 cells was examined in serum-free medium. Among growth factors examined, human insulin and insulin-like growth factor 1 (IGF-1), which were produced by gene engineering techniques, stimulated the growth of metastatic NL-17 and NL-44 cells as determined by thymidine incorporation and cell counts. DNA synthesis and cell proliferation of the high-metastatic NL-17 was stimulated to a greater extent by insulin and IGF-1 than those of the low-metastatic NL-44. These findings suggest that circulating growth factors could enhance the formation of tumor metastasis. Scatchard analysis of [125I]IGF-1 binding to NL-17 and NL-44 showed that each cell line had an almost equal number of IGF-1 receptors (1.37 × 105/cell and 1.26 × 105/cell, respectively), which had similar dissociation constants (8.94×10−10M and 9.54×10−10M, respectively). Since the number and affinity of IGF-1 receptors are equivalent between low- and high-metastatic cells, the intracellular events which result in the cell growth after binding of IGF-1 may differ between NL-17 and NL-44 cells.

2The abbreviations used are:

insulin-like growth factor 1


multiplication stimulating activity


epidermal growth factor


fibroblast growth factor


bovine serum albumin

[I25I] insulin

[125I]-(A14)-monoiodinated insulin

[125I] IGF-1

(3-[125I]iodotyrosyl)insulin-like growth factor-1 [3H]thymidine, [methyl-3H]thymidine


transforming growth factor β


Krebs-Ringer phosphate buffer


minimum essential medium


effective concentration of non-labeled growth factor which inhibits the specific binding of labeled growth factor by 50% of the maximum