Apoptosis, Fas and Fas‐ligand expression in melanocytic tumors

Abstract

Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding to its ligand, Fas ligand (Fas-L), has been shown to trigger apoptosis in various cell types. Fas-L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas-L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with the two other tumors. The anti-Fas-L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas-L expression in melanoma cells and apoptosis in MM-infiltrating mononuclear cells was found, suggesting that Fas-L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.

Fas-Mediated Apoptosis of Melanoma Cells and Infiltrating Lymphocytes in Human Malignant Melanomas

“…The major finding of our study was that Fas expression in melanoma cells correlated significantly with the frequency of apoptosis of melanoma cells and that apoptosis of melanoma cells affected the prognosis of melanoma patients. We also found that both melanoma cells and infiltrating lymphocytes can express Fas and FasL in clinical specimens, extending the earlier findings that Fas is expressed in infiltrating lymphocytes (21) and FasL is expressed in melanoma cells (21)(22)(23)(24), though the lymphocyte apoptosis in itself was not significantly related to the prognosis. Therefore, these results indicate that the melanoma cell apoptosis mediated by the Fas-FasL system may affect the growth of melanoma and the prognosis of melanoma patients.…”

“…Recently, investigation of apoptosis of Faspositive lymphocytes induced by FasL-expressing tumor cells has been focused on tumor escape from immunological rejection in various malignant neoplasms, including hepatocellular carcinoma (7), colon cancer (18,35), and melanoma (21,23,24). Hahne (21) reported that FasL-expressing melanoma cells and Fas-positive lymphocytes were found in metastatic melanoma lesions.…”

“…Maeda et al (22) also found that human melanoma cells expressed FasL in primary lesions, whereas there was no expression of FasL in melanocytic nevus cells and normal melanocytes. More recently, it has been reported that FasL-positive melanoma cells and TUNEL-positive lymphocytes were found in primary lesions of human melanomas (23,24). It is possible that melanoma cells may induce apoptosis of lymphocytes mediated by Fas system.…”

Immunosensitization of Melanoma Tumor Cells to Non-MHC Fas-Mediated Killing by MART-1-Specific CTL Cultures

“…2). In contrast to some previous reports, which showed that cell lines derived from melanoma tumors express FasL (42,43), but in agreement with Chappel et al (44), none of the target cell lines tested (T2, M202, M207, and M238) in this study expressed FasL mRNA (Fig. 2).…”

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

“…Given that alteration of apoptosis represents one of the crucial targets in tumor development (Adams and Cory, 1998;Bakker et al, 1999;Levine, 1997;Sprecher et al, 1999), identifying regulatory components, as shown here for TRAF2/GCK, points to additional targets one may consider for design of therapeutic means to treat this tumor type.…”