Regulation of the Expression of E-Cadherin on Human Cancer Cells by γ-Linolenic Acid (GLA)

E-cadherin is a cell to cell adhesion molecule which acts as a suppressor of metastasis. This study examined the effect of gamma-linolenic acid (GLA), a n-6 polyunsaturated fatty acid, on the expression of E-cadherin in human cancer cells. Western blotting studies demonstrated that treatment of cells with GLA for 24 h increased the expression of E-cadherin in lung, colon, breast, melanoma, and liver cancer cells, but not in endothelial cells and fibroblasts. The results were confirmed by immunocytochemistry. In contrast, two other n-6 fatty acids, linoleic acid and arachidonic acid, failed to induce these changes. The increased expression of E-cadherin was correlated with reduced in vitro invasion and increased aggregation, indicating that the increased E-cadherin expression induced by GLA was biologically active. These data add GLA to the short list of E-cadherin up-regulatory factors. The up-regulation of E-cadherin expression in human cancer cells may contribute to the anticancer properties of GLA.

[1]  J. Espada,et al.  Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features. , 1995, The American journal of pathology.

[2]  R. Poulsom,et al.  Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. , 1995, British Journal of Cancer.

[3]  R. Whyte,et al.  E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett's oesophagus. , 1995, British Journal of Cancer.

[4]  D. Rose,et al.  Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. , 1994, Cancer research.

[5]  W. Jiang,et al.  Molecular and cellular basis of cancer invasion and metastasis: Implications for treatment , 1994, The British journal of surgery.

[6]  M. Mareel,et al.  Tamoxifen restores the E-cadherin function in human breast cancer MCF-7/6 cells and suppresses their invasive phenotype. , 1994, Cancer research.

[7]  M. Sporn,et al.  Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen. , 1994, Cancer research.

[8]  H. Höfler,et al.  E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. , 1994, Cancer research.

[9]  W. Birchmeier,et al.  Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. , 1994, Biochimica et biophysica acta.

[10]  A. Berchuck,et al.  Mutations of the E–cadherin gene in human gynecologic cancers , 1994, Nature Genetics.

[11]  D. Bani,et al.  Relaxin influences growth, differentiation and cell‐cell adhesion of human breast‐cancer cells in culture , 1994, International journal of cancer.

[12]  M. Mareel,et al.  Enlarged cell-associated proteoglycans abolish E-cadherin functionality in invasive tumor cells. , 1994, Cancer research.

[13]  M. Mareel,et al.  Downregulation in vivo of the invasion-suppressor molecule E-cadherin in experimental and clinical cancer. , 1993, Princess Takamatsu symposia.

[14]  F. Révillion,et al.  Effect of calcium on e-cadherin expression in breast-tumor cells. , 1994, International journal of oncology.

[15]  M. Peifer.  Cancer, catenins, and cuticle pattern: a complex connection. , 1993, Science.

[16]  M. Takeichi.  Cadherins in cancer: implications for invasion and metastasis. , 1993, Current opinion in cell biology.

[17]  R. Kemler.  From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. , 1993, Trends in genetics : TIG.

[18]  M. Takeichi,et al.  Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. , 1993, Cancer research.

[19]  Miller Fr.  Immune mechanisms in the sequential steps of metastasis. , 1993 .

[20]  F. Miller.  Immune mechanisms in the sequential steps of metastasis. , 1993, Critical reviews in oncogenesis.

[21]  C. Parish,et al.  A basement‐membrane permeability assay which correlates with the metastatic potential of tumour cells , 1992, International journal of cancer.

[22]  M. Mareel,et al.  Tumour invasion: effects of cell adhesion and motility. , 1992, Trends in cell biology.

[23]  S. Fukushima,et al.  Anticancer effects of free polyunsaturated fatty acids in an oily lymphographic agent following intrahepatic arterial administration to a rabbit bearing VX-2 tumor. , 1992, Cancer research.

[24]  W. Birchmeier,et al.  E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. , 1991, Cancer research.

[25]  D. Rose,et al.  Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. , 1991, Journal of the National Cancer Institute.

[26]  R. Tiwari,et al.  Modulation of gene expression by selected fatty acids in human breast cancer cells. , 1991, Anticancer research.

[27]  M. J. Newman.  Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Wilson,et al.  Molecular aspects of the metastatic cascade. , 1989, Biochimica et biophysica acta.

[29]  L. Liotta,et al.  Biochemical mechanisms of tumor invasion and metastases. , 1988, Advances in experimental medicine and biology.

[30]  K. Erickson,et al.  Enhancement of metastasis from a transplantable mouse mammary tumor by dietary linoleic acid. , 1987, Cancer research.

[31]  Y Iwamoto,et al.  A rapid in vitro assay for quantitating the invasive potential of tumor cells. , 1987, Cancer research.

[32]  L. Liotta.  Biochemical mechanisms of tumor invasion and metastases. , 1987, Clinical physiology and biochemistry.

[33]  D F Horrobin,et al.  Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids. , 1986, Journal of the National Cancer Institute.

[34]  M. Takeichi,et al.  Functional correlation between cell adhesive properties and some cell surface proteins , 1977, The Journal of cell biology.