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

Regulation of CD95 (Apo-1/Fas) ligand and receptor expression in squamous-cell carcinoma by interferon-γ and cisplatin
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DOI:
10.1002/(sici)1097-0215(19990209)80:4
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发表时间:
1999-02-09
影响因子:
6.4
通讯作者:
Häussinger, D
Häussinger, D
中科院分区:
医学1区
文献类型:
--
作者:
Moers, C;Warskulat, U;Häussinger, D

文献摘要

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CD95(载脂蛋白i /Fas)配体(CD95L)在多种恶性肿瘤中均有表达。在人外阴鳞状细胞癌(SCC)原代细胞系中,从mRNA和蛋白水平研究了顺铂(CDDP)和IFN γ对CD95L及其2个受体亚型CD95跨膜(CD95tm)和CD95可溶性受体表达的影响。CDDP和IFN γ分别使原代细胞系中CD95L mRNA水平升高6倍和1.7倍,相比之下,CD95tm mRNA水平在CDDP的作用下降低,但在IFN γ的作用下升高8倍,SCC细胞表达的CD95L在功能上是相关的,因为这些细胞能够在SCC患者的自体淋巴细胞中诱导cd95特异性凋亡。因此,CD95L在SCC中的表达可能有助于肿瘤相关的免疫抑制,这可能是由CDDP和IFN γ调节的。在原发性SCC肿瘤样本中,CD95L在侵袭性肿瘤组织与周围间质细胞交界区域表达增强,CD95L局部受限的过表达与侵袭性瘤舌附近凋亡间质细胞的排列一致,提示CD95L可能是侵袭因子。(C) 1999 Wiley-Liss, Inc。
CD95 (Apo-I/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 gamma 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 gamma 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 gamma 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 gamma. 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. (C) 1999 Wiley-Liss, Inc.