EXPRESSION OF APO-1 (CD95), A MEMBER OF THE NGF/TNF RECEPTOR SUPERFAMILY, IN NORMAL AND NEOPLASTIC COLON EPITHELIUM

被引:293
作者
MOLLER, P
KORETZ, K
LEITHAUSER, F
BRUDERLEIN, S
HENNE, C
QUENTMEIER, A
KRAMMER, PH
机构
[1] UNIV HEIDELBERG, DEPT SURG, D-69120 HEIDELBERG, GERMANY
[2] GERMAN CANC RES CTR, DIV IMMUNOGENET, TUMOR IMMUNOL PROGRAM, D-69120 HEIDELBERG, GERMANY
关键词
D O I
10.1002/ijc.2910570314
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
APO-1 is a 48-kDa cell-membrane protein identical to the Fas antigen now designated CD95. It is a member of the NGF/TNF receptor superfamily. Anti-APO-1 monoclonal antibody induces apoptosis in a variety of cell types expressing this antigen. We immunohistochemically investigated APO-1 expression in normal colon mucosa, 20 adenomas, 258 colon carcinomas and 10 liver metastases and carried out in vitro studies using a panel of colon-carcinoma cell lines. Immunohistochemically, APO-1 was regularly expressed at the basolateral membrane of normal colon epithelia. In a minor fraction of colon adenomas and in 39.1% of colon carcinomas APO-1 expression was diminished and in 48.1% of carcinomas, predominantly of the nonmucinous type, APO-1 expression was completely abrogated. The normal level of APO-1 in carcinomas was correlated with the mucinous type. Reduced/lost APO-1 expression was more frequent in rectal carcinomas. Complete loss of APO-1 was more frequent in tumors that had already metastasized. APO-1 expression in liver metastases essentially corresponded to that of the primary tumors. Comparative analysis with data from previous studies revealed that the model of APO-1 expression is correlated with that of HLA-A,B,C./beta(2)m, HLA-DR, HLA-D-associated invariant chain and of the secretory component. Surface expression of APO-1 was heterogeneous in colon-carcinoma cell lines; SW480 expressed considerable amounts of APO-1 on all cells, while HT-29 constitutively did less so and only in a minority of cells. Surfaces density of APO-1 and the fraction of positive cells in HT-29 was enhanced by interferon-gamma (IFN-gamma) and, additively, by tumor necrosis factor-alpha (TNF-alpha), whereas in SW480 APO-1 expression was not modulated by these cytokines. We conclude that neoplastic transformation of colon epithelium often leads to a loss of the physiologic, high level of surface APO-1 by giving rise either to a stable lack of APO-1 or to an IFN-gamma/TNF-alpha-sensitive phenotype of inducible APO-1 expression. (C) 1994 Wiley-Liss, Inc.
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页码:371 / 377
页数:7
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