Complement resistance of tumor cells:: Basal and induced mechanisms
Complement resistance of tumor cells:: Basal and induced mechanisms
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DOI：
10.1016/s0161-5890(99)00115-7
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发表时间：
1999-09-01
影响因子：
3.6
通讯作者：
Kirschfink, M
中科院分区：
文献类型：
--
作者：
Jurianz, K;Ziegler, S;Kirschfink, M
临床和实验研究表明，补体可能在肿瘤细胞毒性中起作用。然而，补体介导的肿瘤细胞裂解的效率受到各种保护机制的阻碍，这些保护机制可分为两类：基础机制和诱导机制。基础机制在细胞中自发表达，不需要事先激活，而诱导机制在细胞受到细胞因子、激素、药物或补体和其他孔隙形成物的亚溶剂量刺激时形成。膜相关补体调节蛋白，如CD55 （DAF，衰变加速因子）、CD46 （MCP，膜辅助因子蛋白）、CD35 （CR1，补体受体1型）和CD59，作为一种重要的自我保护机制，使自体细胞对补体的作用不敏感，在某些肿瘤上出现过表达。此外，肿瘤细胞分泌几种可溶性补体抑制剂。肿瘤细胞也可能表达降解补体蛋白的蛋白酶，如C3，或能磷酸化补体成分的外泌蛋白激酶，如C9。除了这种基础抵抗外，有核细胞在一定程度上通过去除表面的膜攻击复合物（MAC）来抵抗补体损伤。几种生化途径，包括蛋白质磷酸化、g蛋白活化和磷酸肌苷的转换，都与补体抗性有关。钙离子内流和蛋白激酶C （PKC）和丝裂原活化蛋白激酶（MAPK）的激活也被证明与补体诱导的抗裂解能力增强有关。完全阐明基础和诱导肿瘤细胞耐药的分子机制将有助于开发干扰这些逃避机制和使用细胞毒性补体系统对抗肿瘤细胞的策略。1999爱思唯尔科学有限公司版权所有。
Clinical and experimental studies have suggested that complement may play a role in tumor cytotoxicity. However, the efficiency of complement-mediated tumor cell lysis is hampered by various protective mechanisms, which may be divided into two categories: basal and induced mechanisms. The basal mechanisms are spontaneously expressed in cells without a need for prior activation, whereas the induced mechanisms develop in cells subjected to stimulation with cytokines, hormones, drugs or with sublytic doses of complement and other pore-formers. Membrane-associated complement regulatory proteins, such as CD55 (DAF, Decay-Accelerating Factor), CD46 (MCP, Membrane Cofactor Protein), CD35 (CR1, Complement Receptor type 1) and CD59, which serve as an important mechanism of self protection and render autologous cells insensitive to the action of complement, appear to be over-expressed on certain tumors. Furthermore, tumor cells secrete several soluble complement inhibitors. Tumor cells may also express proteases that degrade complement proteins, such as C3, or ecto-protein kinases which can phosphorylate complement components, such as C9. Besides this basal resistance, nucleated cells resist, to some extent, complement damage by removing the membrane attack complexes (MAC) from their surface. Several biochemical pathways, including protein phosphorylation, activation of G-proteins and turnover of phosphoinositides have been implicated in resistance to complement. Calcium ion influx and activation of protein kinase C (PKC) and of mitogen-activated protein kinase (MAPK) have also been demonstrated to be associated with the complement-induced enhanced resistance to lysis. The complete elucidation of the molecular mechanisms involved in basal and induced tumor cell resistance will enable the development of strategies for interfering with these evasion mechanisms and the use of the cytotoxic complement system against tumor cells. (C) 1999 Elsevier Science Ltd. All rights reserved.