Plasma Fas ligand, an inducer of apoptosis, and plasma soluble Fas, an inhibitor of apoptosis, in advanced melanoma.
The transmembrane receptor Fas/APO-1, together with its protein-binding partner (Fas ligand), is a key regulator of programmed cell death and induces apoptosis when it binds Fas ligand (FasL) or soluble Fas ligand (sFasL). However, soluble Fas (sFas) blocks apoptosis by inhibiting binding between Fas and FasL or sFasL. At present, the status of sFas and sFasL in metastatic malignant melanoma remains unknown. This study sought to evaluate the relationship between plasma levels of sFas and/or sFasL and clinical response in 45 metastatic malignant melanoma patients treated by biochemotherapy. sFas and sFasL were measured by specific enzyme-linked immunosorbent assay (ELISA) tests in the sera from patients and 34 healthy donors. Overall, sFas and sFasL levels in patients were significantly higher (P < 0.0001) than in healthy donors. Before the biochemotherapy treatment the sFas level was about the same in biochemorefractory (n = 26) as in responder patients (n = 19). In contrast, the sFasL level was very high only in biochemorefractory patients. At the end of the treatment, in biochemorefractory patients the sFas level was extremely significantly increased (P < 0.0001) and a significant decrease in the plasma levels of sFasL was observed (P = 0.0002). In responder patients, no change in sFas and sFasL was detected. In conclusion, elevated levels of sFas and sFasL might be associated with poor prognosis in advanced melanoma; their possible role in the regulation of apoptosis in influencing the response to biochemotherapy should be further explored.
Mouawad
R
R
Medical Oncology Department, Salpetrière Hospital, Paris, France. roger.mouawad@psl.ap-hop-paris.fr
Khayat
D
D
Soubrane
C
C
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012016:Reference Values; D012680:Sensitivity and Specificity; D019014:fas Receptor / Q000097:blood*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D007770:L-Lactate Dehydrogenase