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 x 10(5)/cell and 1.26 x 10(5)/cell, respectively), which had similar dissociation constants (8.94 x 10(-10) M and 9.54 x 10(-10) M, 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.
Koenuma
M
M
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Yamori
T
T
Tsuruo
T
T
D000230:Adenocarcinoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D011956:Receptors, Cell Surface / Q000032:analysis; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I