Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. 1995 Apr; 71(4): 744–752.
PMCID: PMC2033731

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987 Jun 15;47(12):3239–3245. [PubMed]
  • August DA, Ottow RT, Sugarbaker PH. Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev. 1984;3(4):303–324. [PubMed]
  • Bégin ME, Ells G, Das UN, Horrobin DF. 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]
  • Bégin ME, Ells G, Horrobin DF. 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. [PubMed]
  • Behrens J, Weidner KM, Frixen UH, Schipper JH, 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. [PubMed]
  • Botha JH, Robinson KM, Ramchurren N, Norman RJ. 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. [PubMed]
  • 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]
  • Donaldson GA, Welch JP. Management of cancer of the colon. Surg Clin North Am. 1974 Jun;54(3):713–731. [PubMed]
  • Eisenberg B, Decosse JJ, 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. [PubMed]
  • Falconer JS, Ross JA, Fearon KC, Hawkins RA, O'Riordain MG, Carter DC. 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. [PMC free article] [PubMed]
  • Furukawa T, Watanabe M, Kubota T, Kase S, Fujita S, Yamamoto T, Saikawa Y, Kuo TH, Tanino H, Kurihara N, et al. 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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]
  • Honn KV, Nelson KK, Renaud C, Bazaz R, Diglio CA, Timar J. Fatty acid modulation of tumor cell adhesion to microvessel endothelium and experimental metastasis. Prostaglandins. 1992 Nov;44(5):413–429. [PubMed]
  • Hussey HJ, Tisdale MJ. 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Jiang WG, Lloyds D, Puntis MC, Nakamura T, Hallett MB. Regulation of spreading and growth of colon cancer cells by hepatocyte growth factor. Clin Exp Metastasis. 1993 May;11(3):235–242. [PubMed]
  • Liotta LA. Biochemical mechanisms of tumor invasion and metastases. Clin Physiol Biochem. 1987;5(3-4):190–199. [PubMed]
  • McIllmurray MB, 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Mohler JL, Broskie EN, Ranparia DJ, Sharief Y, Coleman WB, Smith GJ. Cancer cell motility-inhibitory protein in the Dunning adenocarcinoma model. Cancer Res. 1992 Apr 15;52(8):2349–2352. [PubMed]
  • Newman MJ. 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. [PMC free article] [PubMed]
  • Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, Takatsuka Y, Matsuyoshi N, Hirano S, Takeichi M, et al. 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]
  • Parish CR, Jakobsen KB, Coombe DR. A basement-membrane permeability assay which correlates with the metastatic potential of tumour cells. Int J Cancer. 1992 Sep 30;52(3):378–383. [PubMed]
  • Rose DP, Connolly JM, Meschter CL. 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. [PubMed]
  • Rosen EM, Meromsky L, Setter E, Vinter DW, Goldberg ID. 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. [PubMed]
  • Schiffmann E. Motility as a principal requirement for metastasis. Cancer Invest. 1990;8(6):673–674. [PubMed]
  • Schipper JH, Frixen UH, 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]
  • Shiozaki H, Tahara H, Oka H, Miyata M, Kobayashi K, Tamura S, Iihara K, Doki Y, Hirano S, Takeichi M, et al. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 1991 Jul;139(1):17–23. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Takeda S, Horrobin DF, Manku M, Sim PG, 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]
  • Takeda S, Sim PG, Horrobin DF, Sanford T, Chisholm KA, 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]
  • Tiwari RK, Mukhopadhyay B, Telang NT, Osborne MP. Modulation of gene expression by selected fatty acids in human breast cancer cells. Anticancer Res. 1991 Jul-Aug;11(4):1383–1388. [PubMed]
  • Van der Merwe CF, Booyens J, Katzeff IE. 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]
  • van der Merwe CF, Booyens J, Joubert HF, van der Merwe CA. 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. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...