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热休克蛋白60的表达、新定位、功能以及癌症诊断与治疗的前景

Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy.

作者信息

Cappello Francesco, Conway de Macario Everly, Marasà Lorenzo, Zummo Giovanni, Macario Alberto J L

机构信息

Department of Experimental Medicine, University of Palermo, Palermo, Italy.

出版信息

Cancer Biol Ther. 2008 Jun;7(6):801-9. doi: 10.4161/cbt.7.6.6281. Epub 2008 May 13.

DOI:10.4161/cbt.7.6.6281
PMID:18497565
Abstract

Hsp60 in eukaryotes is considered typically a mitochondrial chaperone (also called Cpn60) but in the last few years it has become clear that it also occurs in the cytosol, the cell surface, the extracellular space, and in the peripheral blood. Studies with prokaryotic models have shown that Hsp60 plays a role in assisting nascent polypeptides to reach a native conformation, and that it interacts with Hsp10 (which also resides in the mitochondria and is also named Cpn10). In addition to its role in polypeptide folding in association with Hsp10, other functions and interacting molecules have been identified for Hsp60 in the last several years. Some of these newly identified functions are associated with carcinogenesis, specifically with tumor cell survival and proliferation. Thus, assessing the levels of Hsp60 in tumor cells and in sera of cancer patients is becoming an attractive area of investigation aiming at the development of means for practical applications in clinical oncology. Since Hsp60 participates in extracellular molecular interactions and cell signalling and also in key intracellular pathways of some types of tumor cells, the idea of using Hsp60 in anti-cancer therapy (chaperonotherapy) is being investigated. The Hsp could be used either as an anticancer agent alone or in combination with tumor antigens, or as target for anti-chaperone compounds. In this article, a brief review is presented of representative research efforts aimed at assessing Hsp60 in a variety of tumors with the purpose of illustrating possible implications and applications for making early and differential diagnoses, assessing prognosis, monitoring response to treatment, and for developing novel anti-cancer strategies.

摘要

真核生物中的热休克蛋白60(Hsp60)通常被认为是一种线粒体伴侣蛋白(也称为Cpn60),但在过去几年中,越来越清楚的是它也存在于细胞质、细胞表面、细胞外空间和外周血中。对原核生物模型的研究表明,Hsp60在协助新生多肽达到天然构象方面发挥作用,并且它与Hsp10相互作用(Hsp10也存在于线粒体中,也称为Cpn10)。除了与Hsp10一起在多肽折叠中发挥作用外,在过去几年中还确定了Hsp60的其他功能和相互作用分子。这些新确定的功能中有些与致癌作用有关,特别是与肿瘤细胞的存活和增殖有关。因此,评估肿瘤细胞和癌症患者血清中Hsp60的水平正成为一个有吸引力的研究领域,旨在开发在临床肿瘤学中实际应用的手段。由于Hsp60参与细胞外分子相互作用和细胞信号传导,也参与某些类型肿瘤细胞的关键细胞内途径,因此正在研究将Hsp60用于抗癌治疗(伴侣蛋白疗法)的想法。Hsp可以单独用作抗癌剂,或与肿瘤抗原联合使用,或作为抗伴侣蛋白化合物的靶点。在本文中,将简要回顾旨在评估各种肿瘤中Hsp60的代表性研究工作,目的是说明在进行早期和鉴别诊断、评估预后、监测治疗反应以及开发新型抗癌策略方面的可能意义和应用。

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