• Open Access

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

Authors


Abstract

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:
IGF-1

insulin-like growth factor 1

MSA

multiplication stimulating activity

EGF

epidermal growth factor

FGF

fibroblast growth factor

BSA

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

TGFβ

transforming growth factor β

KRP

Krebs-Ringer phosphate buffer

MEM

minimum essential medium

EC50′

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

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