Differential increase of Fas ligand expression on metastatic and thin or thick primary melanoma cells compared with interleukin-10.
Fas ligand (FasL), a cell surface molecule belonging to the tumour necrosis factor family, binds to its receptor Fas and thus induces apoptosis of Fas-bearing cells such as activated lymphocytes. In this paper, we report the expression of FasL on melanoma cell lines and patient tumour specimens, and compare it with the expression of interleukin-10 (IL-10), a putative immunosuppressive factor. Apoptosis of Fas-bearing Jurkat cells was increased after interferon-alpha treatment of the FasL-positive melanoma cell line A375, suggesting a regulation of FasL function. We also tested whether FasL and IL-10 were ever co-expressed. Immunohistochemistry studies showed that IL-10 expression was highly positive in the same tumour samples which expressed FasL. In the melanoma patients with thin primaries, 10 of the 12 primaries and six of the seven metastatic lesions were positive for IL-10. In the melanoma patients with thick primaries (> 0.75 mm), four of the five primary lesions and nine of the 10 metastatic lesions were positive for IL-10. In contrast, FasL was generally negative in primary tumours and positive in metastatic tumours. In the thin primary melanoma patients, two of the 12 primaries and five of the seven metastatic tumours were positive for FasL. From the thick melanomas, one of the five primaries and five of the 10 metastatic lesions were positive for FasL. The function of melanoma-derived FasL was confirmed by four different cytotoxicity assays.
Ekmekcioglu
S
S
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Okcu
M F
MF
Colome-Grimmer
M I
MI
Owen-Schaub
L
L
Buzaid
A C
AC
Grimm
E A
EA
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053222:Fas Ligand Protein; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology; D019169:Jurkat Cells; D008545:Melanoma / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016898:Interferon-alpha; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma