A comparative study of Fas and Fas-ligand expression during melanoma progression

Impaired regulation of apoptosis is known to be associated with the development of various cancers. Fas receptor (APO-1/CD95) binding to its ligand, Fas-ligand (Fas-L), has been shown to trigger apoptosis in various cell types.

In this study, we examined CD95 and Fas-L expression on primary and metastatic melanoma cells from patients to investigate a potential correlation between these measures of apoptosis and different disease stages.

Primary melanoma cells were obtained after surgical resection from 19 patients and metastatic cells from fine-needle aspiration of lymph nodes or palpable subcutaneous lesions in 25 patients. Normal skin cells were obtained at skin biopsy of 10 healthy donors.

Flow cytometric analysis revealed that CD95 and Fas-L expression was detected in all the kinds of cell studied. In whole cell suspensions, CD95 expression was significantly higher (P < 0.0001) in normal skin cells than in melanoma cells, whatever the stage studied. By contrast, we observed an increase in Fas-L expression in melanoma cells compared with normal ones. Subsequently, using a double staining method, we studied these measures on HMB45+ cells, a specific marker for melanoma cells, and found that CD95 expression was significantly higher (P = 0.0005) in primary than in metastatic cells while Fas-L expression was significantly increased (P = 0. 0004) in metastatic compared with primary cells. Furthermore, a relationship was found between CD95 or Fas-L expression and Breslow thickness; as primary melanoma thickness progressively increased, the percentage of HMB45+ CD95+ cells decreased while that of HMB45+ Fas-L+ cells concurrently increased.

These results suggest that downregulation of CD95 and upregulation of Fas-L in melanoma might be considered as concomitant with disease progression.