Expression of the c-Met Proteins in Malignant Skin Cancers

Abstract

Background: The expression of c-Met is substantially elevated in most malignant human cancers. We therefore searched for c-Met expression and compared the expression level among malignant skin cancers.

Objective: The aim of this study was to determine the c-Met expression pattern and the protein expression level in selected malignant cutaneous tumors.

Methods: G361 cells (malignant melanoma cell line) and A431 cells (squamous cell carcinoma cell line) were cultured and analyzed, using immunoprecipitation and Western blot analysis, for expression of c-Met. Additionally, 16 separate specimens of malignant melanomas (MMs), 16 squamous cell carcinomas (SCCs), 16 basal cell carcinomas (BCCs) and 16 normal tissues were analyzed for the expression of c-Met using immunohistochemical studies.

Results: Based on cultured cell immunoprecipitation and Western blot analysis, both A431 cells and G361 cells expressed c-Met, however, c-Met was expressed substantially more in G361 cells. Immunohistochemical examination of c-Met showed that it was over-expressed in all malignant skin cancers. In addition, c-Met expression was more increased in MM compared to other cancers.

Conclusion: In our study, c-Met is involved in malignant skin cancer development and the level of its expression is thought to be related to the degree of malignancy in melanoma cancers.

Keywords: Hepatocyte growth factor (HGF); Skin cancers; c-Met expression.

Fig. 1

The Immunoprecipitation and subcellular fraction Western blot assay in the immunoprecipitates. Based on immunoprecipitate analysis involving c-Met expression in A431 cells and G361 cells, c-Met expression was observed in both cell lines, but G361 cells were more strongly expressed. In a subcellular Western blot analysis of c-Met expression study, c-Met expression was found in the cytoplasm. A431: squamous cell carcinoma cell line, G361: malignant melanoma cell line, C: cytoplasm, N: nucleus.

Fig. 2

Immunohistochemical analysis of c-Met expression in (A) normal skin tissue, (B) squamous cell carcinoma, (C) basal cell carcinoma, and (D) malignant melanoma. All malignant skin cancers displayed c-Met expression, but malignant melanoma was expressed more strongly (A: ×100, B, C, D: ×200).

Fig. 3

Immunohistochemical analysis of c-Met expression in malignant melanomas (MMs), squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), and normal human skin. c-Met was strongly expressed in malignant melanomas, while the c-Met was moderately expressed in SCCs and slightly expressed in BCCs. The c-Met was hardly expressed in normal human skin tissues.

Fig. 4

(A) Immunohistochemical analysis of c-Met expression in superficial malignant melanoma, and (B) deeper invasive malignant melanoma tissues. Malignant melanomas have stronger positive staining than other cancers. Indeed, deeper melanoma tissues which had increased breslow level melanomas are observed to have more increased positive staining to the immunohistochemicals (×400).