Effect of endogenous interleukin-6 on Fas (APO-1/CD95) receptor expression in advanced melanoma patients.
Interleukin-6 (IL-6) has been shown to support either autocrine or paracrine growth in melanoma, and may prevent programmed cell death in different cell types. We have previously demonstrated that the endogenous IL-6 level is significantly correlated with tumor burden and nonresponse to biochemotherapy in metastatic malignant melanoma patients. In the present study, we investigated the relationship between endogenous IL-6 and apoptosis signal through Fas (APO-1/CD95) receptor expression in 9 responder and 15 refractory patients with metastatic disease treated by biochemotherapy. Before any treatment, double immunostaining demonstrated that 61.5% of the tumor cells were HMB45+CD95+. At day 49 in refractory patients, a significant decrease (p = 0.04) of total Fas expression was observed. Furthermore, a significant reduction (p = 0.032) in the percentage of HMB45+CD95* cells occurred. An 11-fold increase in serum IL-6 level was detected (p < 0.002). This increase was negatively correlated (r = -0.2, p = 0.008) with the decrease in total Fas expression. However, in responding patients, no detectable decrease in Fas expression was observed, while a very low increase in serum IL-6 (2-fold) was detected. These results suggest that the increased endogenous IL-6 level in refractory patients may inhibit apoptosis via modulation of Fas expression. These preliminary results must be interpreted with caution, and further study with a greater number of patients is needed to understand the mechanism by which IL-6 inhibits apoptosis in melanoma.
Mouawad
R
R
Medical Oncology Department, Salpêtrière Hospital, Paris, France. roger.mouawad@psl.ap-hop-paris.fr
Antoine
E C
EC
Khayat
D
D
Soubrane
C
C
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D017209:Apoptosis; D002945:Cisplatin / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D000951:Antigens, Neoplasm; D007376:Interleukin-2; D015850:Interleukin-6; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D002945:Cisplatin