Heat shock proteins: Stress proteins with Janus-like properties in cancer
Heat shock proteins: Stress proteins with Janus-like properties in cancer
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DOI：
10.1080/02656730701858305
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Ciocca, Daniel R.
中科院分区：
文献类型：
--
作者：
Calderwood, Stuart K.;Ciocca, Daniel R.
热休克蛋白（HSPs）首先被鉴定为在所有细胞生物中赋予对物理应激（如升高的温度）的抗性的应激蛋白。热休克蛋白在应激后迅速升高，并赋予耐温表型。耐热性取决于HSP作为分子伴侣和防止聚集的能力以及HSP 27和HSP 70作为细胞死亡途径的广谱抑制剂的能力。HSP表达在癌症中变得失调，导致表达升高。HSP表达升高通过抑制程序性细胞死亡（Hsp27、Hsp70）和促进自主生长（Hsp90）促进癌症，并导致对化疗和热疗的抗性。肿瘤热休克蛋白具有另一种可用于治疗的特性。它们具有免疫原性，可用于形成抗癌疫苗的基础。因此，HSP水平的升高可能对肿瘤生长具有竞争性影响，这是肿瘤细胞存活所需的，但由于其免疫原性，对癌细胞具有危害。这种二分法也反映在治疗中用于靶向HSP的方法上。药理学方法被用来抑制肿瘤HSP的活性或表达。免疫学方法旨在增加细胞和组织中的HSP水平，目的是增加肿瘤抗原向免疫系统的呈递。
Heat shock proteins (HSPs) were first identified as stress proteins that confer resistance to physical stresses such as elevated temperatures in all cellular organisms. HSPs are rapidly elevated after stress and confer a temperature resistant phenotype. Temperature resistance is dependent on the ability of HSPs to function as molecular chaperones and prevent aggregation and on the capacity of Hsp27 and Hsp70 to act as wide spectrum inhibitors of the cell death pathways. HSP expression becomes deregulated in cancer leading to elevated expression. Elevated HSP expression promotes cancer by inhibiting programmed cell death (Hsp27, Hsp70) and by promoting autonomous growth (Hsp90) and leads to resistance to chemotherapy and hyperthermia. Tumor HSPs have another property that can be exploited in therapy. They are immunogenic and can be used to form the basis of anticancer vaccines. Elevation in HSP levels may thus have competing effects in tumor growth, being required for tumor cell survival but conferring a hazard for cancer cells due to their immunogenic properties. This dichotomy is also reflected by the approaches used to target HSP in therapy. Pharmacological approaches are being employed to inhibit activity or expression of tumor HSP. Immunological approaches aim at increasing HSP levels in cells and tissues with the aim of increasing tumor antigen presentation to the immune system.