Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Cell Cycle. 2010 Feb 15;9(4):676-82. doi: 10.4161/cc.9.4.10782. Epub 2010 Mar 2.
We consider the novel means of attack and defense in the host versus cancer combat that involve interactions between widespread multifunctional proteins, focusing on the aspects that may seem paradoxical in the framework of established notions. Particularly, we show that a protein broadly known for its protective functions such as Hsp70 can make a tumoricidal "binary weapon" with another nontoxic protein Tag7 (PGRP-S); that the same Hsp70, a ubiquitous intracellular chaperone, when expressed on the MHC-negative tumor cell surface, can itself be the hallmark of immune evasion rather than a primordial MHC substitute; that a device functionally equivalent to the T-cell receptor (Tag7-Centered Recognizer) can be assembled of components in no way related to the classical pathways of T-cell-mediated immunity, and operate where the orthodox immunosurveillance fails; and that one and the same protein Mts1 (S100A4) under different circumstances may work as "reactive armor" of a tumor cell against humoral agents and as a vital part of the T-cell machinery aimed against immunoevasive cells, i.e., perform both prometastatic and antimetastatic functions.
我们考虑了宿主与癌症斗争中涉及广泛多功能蛋白质相互作用的新型攻击和防御手段，重点关注在既定概念框架下看似矛盾的方面。特别是，我们表明，一种广泛以其保护功能而闻名的蛋白质（如 Hsp70）可以与另一种无毒蛋白质 Tag7（PGRP-S）形成一种具有杀伤肿瘤作用的“二元武器”；同样的 Hsp70，一种普遍存在的细胞内伴侣，当其在 MHC 阴性肿瘤细胞表面表达时，本身可能是免疫逃逸的标志，而不是原始 MHC 的替代品；一种功能上等同于 T 细胞受体（Tag7 中心识别器）的装置可以由与 T 细胞介导的免疫的经典途径无关的组件组装而成，并在正统免疫监视失败的地方发挥作用；而且，在不同的情况下，一种相同的蛋白质 Mts1（S100A4）可能既作为肿瘤细胞抵抗体液因子的“反应装甲”，又作为针对免疫逃逸细胞的 T 细胞机制的重要组成部分，即发挥促转移和抗转移功能。
