Interleukin 6 downregulates N-cadherin and (alpha)3(beta)1 integrin expression in human melanoma cells.

DG Gil, PhD, a A Litynska, PhD b PM Laidler, PhD c

a,cInstitute of Medical Biochemistry, Medical College, Jagiellonian University, Krakow, bDepartment of Animal Physiology, Jagiellonian University, Krakow, Poland

Cadherins are calcium-dependent transmembrane glycoproteins that mediate cell-cell adhesion. Skin melanocytes express functional P- and E-cadherin, the latter one being primarily responsible for adhesion of human melanocytes to keratinocytes. During melanoma development loss of E-cadherins expression is observed. It is accompanied by a parallel gain of N-cadherin expression, that facilitates migration of melanoma cells from epidermis. Using interleukin 6 we were able to reduce proliferation of melanoma cells and expression of N-cadherin and 31 integrin. Studies were carried out on human melanoma cell lines: WM 35 (RGP); WM 902B (VGP); WM 239 skin metastasis and A 375 metastatic cell line. Expression of cadherins were studied on protein (Western blott) and mRNA levels (RT-PCR) and expression of integrins using flow cytometry (FACS). Expression of N-cadherin was identified on both levels in all studied lines, but E-cadherin was found only in WM 35 cell line at the mRNA level. After incubation with IL-6 we observed decrease of expression of N-cadherin in all cell lines but no changes were observed at the mRNA level. No restoration of E-cadherin was noticed. We conclude that interleukin 6 inhibited growth of melanoma cell lines and downregulated expression of N-cadherin  molecule which induces cell migration, invasion and metastasis. The decrease in its expression was accompanied by diminished expression of another cell adhesion molecule of integrin family - (alpha)3(beta)1  also involved in melanoma cells migration.

KEY WORDS: E-cadherin, N-cadherin, gene expression, melanomas.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Gene Expression, Part 2.