Ciocca Daniel R, Calderwood Stuart K
Oncology Laboratory, Institute of Experimental Medicine and Biology of Cuyo (CRICYT-CONICET), Mendoza, Argentina.
Cell Stress Chaperones. 2005 Summer;10(2):86-103. doi: 10.1379/csc-99r.1.
Heat shock proteins (Hsps) are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. We review the current status of the role of Hsp expression in cancer with special emphasis on the clinical setting. Although Hsp levels are not informative at the diagnostic level, they are useful biomarkers for carcinogenesis in some tissues and signal the degree of differentiation and the aggressiveness of some cancers. In addition, the circulating levels of Hsp and anti-Hsp antibodies in cancer patients may be useful in tumor diagnosis. Furthermore, several Hsp are implicated with the prognosis of specific cancers, most notably Hsp27, whose expression is associated with poor prognosis in gastric, liver, and prostate carcinoma, and osteosarcomas, and Hsp70, which is correlated with poor prognosis in breast, endometrial, uterine cervical, and bladder carcinomas. Increased Hsp expression may also predict the response to some anticancer treatments. For example, Hsp27 and Hsp70 are implicated in resistance to chemotherapy in breast cancer, Hsp27 predicts a poor response to chemotherapy in leukemia patients, whereas Hsp70 expression predicts a better response to chemotherapy in osteosarcomas. Implication of Hsp in tumor progression and response to therapy has led to its successful targeting in therapy by 2 main strategies, including: (1) pharmacological modification of Hsp expression or molecular chaperone activity and (2) use of Hsps in anticancer vaccines, exploiting their ability to act as immunological adjuvants. In conclusion, the present times are of importance for the field of Hsps in cancer, with great contributions to both basic and clinical cancer research.
热休克蛋白（Hsps）在多种人类癌症中过度表达，并与肿瘤细胞的增殖、分化、侵袭、转移、死亡以及免疫系统的识别有关。我们综述了Hsp表达在癌症中作用的当前状况，特别强调临床背景。尽管Hsp水平在诊断层面并无信息价值，但它们在某些组织中是致癌作用的有用生物标志物，并能表明某些癌症的分化程度和侵袭性。此外，癌症患者中Hsp和抗Hsp抗体的循环水平可能有助于肿瘤诊断。此外，几种Hsp与特定癌症的预后有关，最显著的是Hsp27，其表达与胃癌、肝癌、前列腺癌和骨肉瘤的不良预后相关，以及Hsp70，它与乳腺癌、子宫内膜癌、子宫颈癌和膀胱癌的不良预后相关。Hsp表达增加也可能预测对某些抗癌治疗的反应。例如，Hsp27和Hsp70与乳腺癌对化疗的耐药性有关，Hsp27预测白血病患者对化疗反应不佳，而Hsp70表达预测骨肉瘤患者对化疗反应较好。Hsp在肿瘤进展和治疗反应中的作用已导致通过两种主要策略成功地将其作为治疗靶点，包括：（1）对Hsp表达或分子伴侣活性进行药理学修饰，以及（2）在抗癌疫苗中使用Hsps，利用它们作为免疫佐剂的能力。总之，当前对于癌症领域的Hsps来说非常重要，对基础和临床癌症研究都有很大贡献。
