Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Anatomia Umana, University of Palermo, Palermo, Italy.
Curr Pharm Des. 2013;19(3):452-7.
In this minireview we focus on Hsp60 as a target for anticancer therapy. We discuss the new concepts of chaperonopathies and chaperonotherapy and present information on Hsp60 localization in the cell membrane of human tumor cells. We describe novel mechanisms for Hsp60 reaching the extracellular environment that involve membrane-associated stages, as well as data on anti-Hsp60 antibodies found in human sera, both in normal subjects and patients affected by autoimmune diseases. Finally, we discuss possible therapeutic applications of anti-Hsp60 antibodies in cancer treatment, evaluating also side effects on non-tumor cells. In conclusion, the way for investigating Hsp60-targeted anti-tumor therapy is open, at least for those tumors that express Hsp60 on its surface and/or secrete it outside the cell, as is the search for the molecular mechanisms involved in Hsp60 translocation from cytosol to cell membrane: elucidation of this mechanism will greatly facilitate the optimization of chaperonotherapy centered on Hsp60 with anti-tumor efficacy and minimal side effects.
在这篇综述中，我们专注于 Hsp60 作为抗癌治疗的靶点。我们讨论了伴侣蛋白病和伴侣蛋白治疗的新概念，并介绍了 Hsp60 在人肿瘤细胞膜中的定位信息。我们描述了 Hsp60 到达细胞外环境的新机制，包括与膜相关的阶段，以及在正常人和自身免疫性疾病患者的血清中发现的抗 Hsp60 抗体的数据。最后，我们讨论了抗 Hsp60 抗体在癌症治疗中的可能治疗应用，同时评估了对非肿瘤细胞的副作用。总之，至少对于那些在表面表达 Hsp60 并/或在细胞外分泌它的肿瘤，研究针对 Hsp60 的抗肿瘤治疗的方法是可行的，同时也在寻找 Hsp60 从细胞质到细胞膜易位所涉及的分子机制：阐明这一机制将极大地促进以 Hsp60 为中心的伴侣蛋白治疗的优化，以实现抗肿瘤疗效和最小的副作用。
