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Regulation of CD95 (APO-1/ FAS) ligand and receptor expression in squamous-cell carcinoma by interferon-γ and cisplatin

✍ Scribed by Cordula Moers; Ulrich Warskulat; Markus Müschen; Jos Even; Dieter Niederacher; Régis Josien; Ursula Koldovsky; Matthias W. Beckmann; Dieter Häussinger

Publisher
John Wiley and Sons
Year
1999
Tongue
French
Weight
337 KB
Volume
80
Category
Article
ISSN
0020-7136

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✦ Synopsis

CD95 (Apo-1/Fas) ligand (CD95L) expression has been observed in various malignancies. In human primary cell lines from a squamous cell carcinoma (SCC) of the vulva, the effect of cisplatin (CDDP) and IFN␥ on the expression of CD95L and its 2 receptor isoforms, CD95 transmembrane (CD95tm) and CD95 soluble receptor, was studied at the mRNA and protein levels. Addition of CDDP and IFN␥ increased CD95L mRNA levels in the primary cell line 6-fold and 1.7-fold, respectively. In comparison, CD95tm mRNA levels were diminished by CDDP but increased 8-fold upon IFN␥ challenge. CD95L expressed by SCC cells was functionally relevant since these cells were able to induce CD95-specific apoptosis in autologous lymphocytes from the SCC-bearing patient. Thus, CD95L expression in SCC may contribute to tumor-associated immunosuppression, which may be modulated by CDDP and IFN␥. In tumor samples of the primary SCC, CD95L expression was enhanced in the area of the border between invasive tumor tissue and surrounding stroma cells. The locally restricted over-expression of CD95L was congruent with the arrangement of apoptotic stroma cells in the direct vicinity of invading tumor tongues, suggesting a role as invasion factor for CD95L.

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