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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1989 Jan;80(1):51–58. doi: 10.1111/j.1349-7006.1989.tb02244.x

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

Mitsuo Koenuma 1, Takao Yamori 1, Takashi Tsuruo 1,✉
PMCID: PMC5917674  PMID: 2540132

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.

Keywords: Metastasis, Growth factor, IGF‐1, Insulin, Colon carcinoma 26

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REFERENCES

  • 1. ) Fidler , I. I , Gersten , D. M. and Hart , I. R.The biology of cancer invasion and metastasis . Adv. Cancer Res. , 28 , 149 – 250 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Nicolson , G. L. and Winkelhake , J. L.Organ specificity of blood‐borne tumor metastasis determined by cell adhesion ? Nature , 255 , 230 – 232 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Poste , G. and Fidler , I. J.The pathogenesis of cancer metastasis . Nature , 283 , 139 – 146 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Tsuruo , T. , Kawabata , H. , Iida , H. and Yamori , T.Tumor‐induced platelet aggregation and growth promoting factors as determinants for successful tumor metastasis . Clin. Exp. Metastasis , 4 , 25 – 33 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Yamori , T. , Iida , H. , Tsukagoshi , S. and Tsuruo , T.Growth stimulating activity of lung extract on lung‐colonizing colon 26 clones and its partial characterization . Clin. Exp. Metastasis , 6 , 131 – 139 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Sugimoto , Y. , Oh‐hara , T. , Watanabe , M. , Saito , H. , Yamori , T. and Tsuruo , T.Acquisition of metastatic ability in hybridomas between two low metastatic clones of colon adenocarcinoma 26 defective in either platelet‐aggregating activity or in vivo growth potential . Cancer Res. , 47 , 4396 – 4401 ( 1987. ). [PubMed] [Google Scholar]
  • 7. ) Tsuruo , T. , Yamori , T. , Naganuma , K. , Tsukagoshi , S. and Sakurai , Y.Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26 . Cancer Res. , 43 , 5437 – 5442 ( 1983. ). [PubMed] [Google Scholar]
  • 8. ) Fernandez‐Pol , J. A. , Klos , D. J. and Grant , G. A.Purification and biological properties of type β transforming growth factor from mouse transformed cells . Cancer Res. , 46 , 5153 – 5161 ( 1986. ). [PubMed] [Google Scholar]
  • 9. ) Iwamoto , Y. , Wong , K. Y. and Goldfine , I. D.Insulin action in cultured HTC and H35 rat hepatoma cells: receptor binding and hormone sensitivity . Endocrinology , 108 , 44 – 51 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Yamada , Y. and Serrero , G.Characterization of an insulin‐related factor secreted by a teratoma cell line . Biochem. Biophys. Res. Commun. , 135 , 553 – 540 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Heldin , C‐H. , Wasteson , A. and Westermark , B.Interaction of platelet‐derived growth factor with its fibroblast receptor . J. Biol Chem. , 257 , 4216 – 4221 ( 1982. ). [PubMed] [Google Scholar]
  • 12. ) Rodeck , U. , Herlyn , M. , Menssen , H. D. , Furlanetto , R. W. and Koprowski , H.Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors . Int. J. Cancer , 40 , 687 – 690 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Flier , J. S. , Usher , P. and Moses , A. C.Monoclonal antibody to the type 1 insulin‐like growth factor (IGF‐1) receptor blocks IGF‐1 receptor‐mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF‐1 and insulin in human skin fibroblasts . Proc. Natl. Acad. Sci. USA , 83 , 664 – 668 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Clemmons , D. R.Multiple hormones stimulate the production of somatomedin by cultured human fibrosarcoma . J. Clin. Endocrinol. Metab. , 58 , 850 – 856 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Rinderknecht , E. and Humbel , R. E.The amino acid sequence of human insulin‐like growth factor 1 and its structural homology with proinsulin . J. Biol. Chem. , 253 , 2769 – 2776 ( 1978. ). [PubMed] [Google Scholar]
  • 16. ) Zapf , J. , Walter , H. and Froesch , E. R.Radioimmunological determination of insulin like growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia . J. Clin. Invest. , 68 , 1321 – 1330 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Dércole , A. J. , Stiles , A. D. and Underwood , L. E.Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action . Proc. Natl. Acad. Sci. USA , 81 , 935 – 939 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Lund , P. K. , Moats‐Staats , B. M. , Hynes , M. A. , Simmons , J. G. , Jansen , M. , D'Ercole , A. J. , and Van Wyk , J. J.Somatomedin‐C/insulin‐like growth factor‐1 and insulin‐like growth factor‐II mRNAs in rat fetal and adult tissues . J. Biol. Chem. , 261 , 14539 – 14544 ( 1986. ). [PubMed] [Google Scholar]
  • 19. ) Han , V. K. M. , D'Ercole , A. J. and Lund , P. K.Cellular localization of somatomedin (insulin‐like growth factor) messenger RNA in the human fetus . Science , 236 , 193 – 196 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) King , G. L. , Kahn , C. R. , Rechler , M. M. and Nissley , S. P.Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication‐stimulating activity (an insulin like growth factor) using antibodies to the insulin receptor . J. Clin. Invest. , 66 , 130 – 140 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. ) Crettaz , M. and Kahn , C. R.Analysis of insulin action using differentiated and dedifferentiated hepatoma cells . Endocrinology , 113 , 1201 – 1209 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Horak , E. , Darling , D. L. and Tarin , D.Analysis of organ specific effects of metastatic tumor formation by studies in vitro . J. Natl. Cancer Inst. , 76 , 913 – 922 ( 1986. ). [PubMed] [Google Scholar]
  • 23. ) Nicolson , G. L. and Dulski , K. M.Organ specificity of metastatic tumor colonization is related to organ‐selective growth properties of malignant cells . Int. J. Cancer , 38 , 289 – 294 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Price , J. E. , Naito , S. and Fidler , I. J.Growth in an organ microenvironment as a selective process in metastasis . Clin. Exp. Metastasis , 6 , 91 – 102 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Liotta , L. A. , Thorgeirsson , U. P. and Garbisa , S.Role of collagenase in tumor cell invasion . Cancer Metastasis Rev. , 1 , 277 – 288 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Nakajima , M. , Irimura , T. , Di Ferrante , N. and Nicolson , G. L.Metastatic melanoma cell heparanase, characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase . J. Biol. Chem. , 259 , 2283 – 2290 ( 1984. ). [PubMed] [Google Scholar]
  • 27. ) Liotta , L. A.Tumor invasion and metastases—role of the extracellular matrix: Rhodes memorial award lecture . Cancer Res. , 46 , 1 – 7 ( 1986. ). [PubMed] [Google Scholar]
  • 28. ) Humphries , M. J. , Olden , K. and Yamada , K. M.A synthetic peptide fibronectin inhibits experimental metastasis of murine melanoma cells . Science , 233 , 467 – 469 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Iwamoto , Y. , Robey , F. A. , Graf , J. , Sasaki , M. , Kleinman , H. K. , Yamada , Y. and Martin , G. R.YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation . Science , 238 , 1132 – 1134 ( 1981. ). [DOI] [PubMed] [Google Scholar]

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