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. 1995 Apr;71(4):744–752. doi: 10.1038/bjc.1995.145

Inhibition of hepatocyte growth factor-induced motility and in vitro invasion of human colon cancer cells by gamma-linolenic acid.

W G Jiang 1, S Hiscox 1, M B Hallett 1, C Scott 1, D F Horrobin 1, M C Puntis 1
PMCID: PMC2033731  PMID: 7710939

Abstract

In this study we have determined the effects of the n-6 essential fatty acid gamma-linolenic acid (GLA) on the motility and invasive/metastatic nature of the human colon cancer cell lines HT115, HT29 and HRT18. Cell motility was induced by hepatocyte growth factor/scatter factor (HGF/SF) and measured by both colony scattering and dissociation from carrier beads. Invasiveness was measured in vitro by cellular invasion into extracellular matrix. At concentrations up to 100 microM (which had no effect on cell growth over the duration of the experiments) both cell motility and invasion induced by HGF/SF were markedly reduced by GLA and its lithium salt. The attachment of these cells to the extracellular matrix components (Matrigel and fibronectin) was also inhibited. There were also changes in the cell-surface E-cadherin, but not fibronectin receptor at similar concentrations. It is concluded that n-6 essential fatty acids have the ability to inhibit both motility and invasiveness of human colon cancer cells, perhaps by modifying cell-surface adhesion molecules.

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Selected References

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  1. Albini A., Iwamoto Y., Kleinman H. K., Martin G. R., Aaronson S. A., Kozlowski J. M., McEwan R. N. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987 Jun 15;47(12):3239–3245. [PubMed] [Google Scholar]
  2. August D. A., Ottow R. T., Sugarbaker P. H. Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev. 1984;3(4):303–324. doi: 10.1007/BF00051457. [DOI] [PubMed] [Google Scholar]
  3. Behrens J., Weidner K. M., Frixen U. H., Schipper J. H., Sachs M., Arakaki N., Daikuhara Y., Birchmeier W. The role of E-cadherin and scatter factor in tumor invasion and cell motility. EXS. 1991;59:109–126. doi: 10.1007/978-3-0348-7494-6_8. [DOI] [PubMed] [Google Scholar]
  4. Botha J. H., Robinson K. M., Ramchurren N., Norman R. J. The role of prostaglandins in the inhibition of cultured carcinoma cell growth produced by gamma-linolenic acid. Prostaglandins Leukot Essent Fatty Acids. 1989 Feb;35(2):119–123. doi: 10.1016/0952-3278(89)90175-0. [DOI] [PubMed] [Google Scholar]
  5. Bégin M. E., Ells G., Das U. N., Horrobin D. F. Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids. J Natl Cancer Inst. 1986 Nov;77(5):1053–1062. [PubMed] [Google Scholar]
  6. Bégin M. E., Ells G., Horrobin D. F. Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. J Natl Cancer Inst. 1988 Apr 6;80(3):188–194. doi: 10.1093/jnci/80.3.188. [DOI] [PubMed] [Google Scholar]
  7. Doki Y., Shiozaki H., Tahara H., Inoue M., Oka H., Iihara K., Kadowaki T., Takeichi M., Mori T. Correlation between E-cadherin expression and invasiveness in vitro in a human esophageal cancer cell line. Cancer Res. 1993 Jul 15;53(14):3421–3426. [PubMed] [Google Scholar]
  8. Donaldson G. A., Welch J. P. Management of cancer of the colon. Surg Clin North Am. 1974 Jun;54(3):713–731. doi: 10.1016/s0039-6109(16)40344-0. [DOI] [PubMed] [Google Scholar]
  9. Eisenberg B., Decosse J. J., Harford F., Michalek J. Carcinoma of the colon and rectum: the natural history reviewed in 1704 patients. Cancer. 1982 Mar 15;49(6):1131–1134. doi: 10.1002/1097-0142(19820315)49:6<1131::aid-cncr2820490611>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  10. Falconer J. S., Ross J. A., Fearon K. C., Hawkins R. A., O'Riordain M. G., Carter D. C. Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines. Br J Cancer. 1994 May;69(5):826–832. doi: 10.1038/bjc.1994.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Furukawa T., Watanabe M., Kubota T., Kase S., Fujita S., Yamamoto T., Saikawa Y., Kuo T. H., Tanino H., Kurihara N. Significance of in vitro attachment of human colon cancers to extracellular matrix proteins in experimental and clinical liver metastases. J Surg Oncol. 1993 May;53(1):10–16. doi: 10.1002/jso.2930530105. [DOI] [PubMed] [Google Scholar]
  12. Gherardi E., Gray J., Stoker M., Perryman M., Furlong R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5844–5848. doi: 10.1073/pnas.86.15.5844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hayashi Y., Fukushima S., Kishimoto S., Kawaguchi T., Numata M., Isoda Y., Hirano J., Nakano M. Anticancer effects of free polyunsaturated fatty acids in an oily lymphographic agent following intrahepatic arterial administration to a rabbit bearing VX-2 tumor. Cancer Res. 1992 Jan 15;52(2):400–405. [PubMed] [Google Scholar]
  14. Honn K. V., Nelson K. K., Renaud C., Bazaz R., Diglio C. A., Timar J. Fatty acid modulation of tumor cell adhesion to microvessel endothelium and experimental metastasis. Prostaglandins. 1992 Nov;44(5):413–429. doi: 10.1016/0090-6980(92)90137-i. [DOI] [PubMed] [Google Scholar]
  15. Hussey H. J., Tisdale M. J. Effect of polyunsaturated fatty acids on the growth of murine colon adenocarcinomas in vitro and in vivo. Br J Cancer. 1994 Jul;70(1):6–10. doi: 10.1038/bjc.1994.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Isoai A., Goto-Tsukamoto H., Murakami K., Akedo H., Kumagai H. A potent anti-metastatic activity of tumor invasion-inhibiting factor-2 and albumin conjugate. Biochem Biophys Res Commun. 1993 Apr 15;192(1):7–14. doi: 10.1006/bbrc.1993.1374. [DOI] [PubMed] [Google Scholar]
  17. Jiang W. G., Lloyds D., Puntis M. C., Nakamura T., Hallett M. B. Regulation of spreading and growth of colon cancer cells by hepatocyte growth factor. Clin Exp Metastasis. 1993 May;11(3):235–242. doi: 10.1007/BF00121166. [DOI] [PubMed] [Google Scholar]
  18. Liotta L. A. Biochemical mechanisms of tumor invasion and metastases. Clin Physiol Biochem. 1987;5(3-4):190–199. [PubMed] [Google Scholar]
  19. McIllmurray M. B., Turkie W. Controlled trial of gamma linolenic acid in Duke's C colorectal cancer. Br Med J (Clin Res Ed) 1987 May 16;294(6582):1260–1260. doi: 10.1136/bmj.294.6582.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miyake M., Koyama M., Seno M., Ikeyama S. Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody M31-15, which inhibits cell motility. J Exp Med. 1991 Dec 1;174(6):1347–1354. doi: 10.1084/jem.174.6.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mohler J. L., Broskie E. N., Ranparia D. J., Sharief Y., Coleman W. B., Smith G. J. Cancer cell motility-inhibitory protein in the Dunning adenocarcinoma model. Cancer Res. 1992 Apr 15;52(8):2349–2352. [PubMed] [Google Scholar]
  22. Newman M. J. Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5543–5547. doi: 10.1073/pnas.87.14.5543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oka H., Shiozaki H., Kobayashi K., Inoue M., Tahara H., Kobayashi T., Takatsuka Y., Matsuyoshi N., Hirano S., Takeichi M. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993 Apr 1;53(7):1696–1701. [PubMed] [Google Scholar]
  24. Parish C. R., Jakobsen K. B., Coombe D. R. A basement-membrane permeability assay which correlates with the metastatic potential of tumour cells. Int J Cancer. 1992 Sep 30;52(3):378–383. doi: 10.1002/ijc.2910520309. [DOI] [PubMed] [Google Scholar]
  25. Rose D. P., Connolly J. M., Meschter C. L. Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. J Natl Cancer Inst. 1991 Oct 16;83(20):1491–1495. doi: 10.1093/jnci/83.20.1491. [DOI] [PubMed] [Google Scholar]
  26. Rosen E. M., Meromsky L., Setter E., Vinter D. W., Goldberg I. D. Quantitation of cytokine-stimulated migration of endothelium and epithelium by a new assay using microcarrier beads. Exp Cell Res. 1990 Jan;186(1):22–31. doi: 10.1016/0014-4827(90)90205-o. [DOI] [PubMed] [Google Scholar]
  27. Schiffmann E. Motility as a principal requirement for metastasis. Cancer Invest. 1990;8(6):673–674. doi: 10.3109/07357909009018943. [DOI] [PubMed] [Google Scholar]
  28. Schipper J. H., Frixen U. H., Behrens J., Unger A., Jahnke K., Birchmeier W. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991 Dec 1;51(23 Pt 1):6328–6337. [PubMed] [Google Scholar]
  29. Shiozaki H., Tahara H., Oka H., Miyata M., Kobayashi K., Tamura S., Iihara K., Doki Y., Hirano S., Takeichi M. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 1991 Jul;139(1):17–23. [PMC free article] [PubMed] [Google Scholar]
  30. Tada H., Shiho O., Kuroshima K., Koyama M., Tsukamoto K. An improved colorimetric assay for interleukin 2. J Immunol Methods. 1986 Nov 6;93(2):157–165. doi: 10.1016/0022-1759(86)90183-3. [DOI] [PubMed] [Google Scholar]
  31. Takeda S., Horrobin D. F., Manku M., Sim P. G., Ells G., Simmons V. Lipid peroxidation in human breast cancer cells in response to gamma-linolenic acid and iron. Anticancer Res. 1992 Mar-Apr;12(2):329–333. [PubMed] [Google Scholar]
  32. Takeda S., Sim P. G., Horrobin D. F., Sanford T., Chisholm K. A., Simmons V. Mechanism of lipid peroxidation in cancer cells in response to gamma-linolenic acid (GLA) analyzed by GC-MS(I): Conjugated dienes with peroxyl (or hydroperoxyl) groups and cell-killing effects. Anticancer Res. 1993 Jan-Feb;13(1):193–199. [PubMed] [Google Scholar]
  33. Tiwari R. K., Mukhopadhyay B., Telang N. T., Osborne M. P. Modulation of gene expression by selected fatty acids in human breast cancer cells. Anticancer Res. 1991 Jul-Aug;11(4):1383–1388. [PubMed] [Google Scholar]
  34. Van der Merwe C. F., Booyens J., Katzeff I. E. Oral gamma-linolenic acid in 21 patients with untreatable malignancy. An ongoing pilot open clinical trial. Br J Clin Pract. 1987 Sep;41(9):907–915. [PubMed] [Google Scholar]
  35. van der Merwe C. F., Booyens J., Joubert H. F., van der Merwe C. A. The effect of gamma-linolenic acid, an in vitro cytostatic substance contained in evening primrose oil, on primary liver cancer. A double-blind placebo controlled trial. Prostaglandins Leukot Essent Fatty Acids. 1990 Jul;40(3):199–202. doi: 10.1016/0952-3278(90)90098-6. [DOI] [PubMed] [Google Scholar]

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