Laboratory of Oncology, Institute of Experimental Medicine and Biology of Cuyo, Scientific and Technological Centre of Mendoza, National Research Council (CONICET) and Argentina Foundation for Cancer Research, Mendoza, Argentina.
Int J Hyperthermia. 2010;26(8):737-47. doi: 10.3109/02656731003776968. Epub 2010 Sep 21.
The heat shock proteins (HSP) constitute a superfamily of chaperone proteins present in all cells and in all cell compartments, operating in a complex interplay with synergistic/overlapping multiplicity of functions, even though the common effect is cell protection. Several reasons explain the need for investigating HSP in prostate cancer: (1) these molecules function as chaperones of tumorigenesis accompanying the emergence of prostate cancer cells, (2) they appear as useful molecular markers associated with disease aggressiveness and with resistance to anticancer therapies including hormone therapy, radiotherapy, chemotherapy and hyperthermia, and (3) they can be used as targets for therapies. The latter can be accomplished by: (i) interrupting the interaction of HSP (mainly HSPC1) with various client proteins that are protected from degradation when chaperoned by the HSP; (ii) using the chaperone and adjuvant capabilities of certain HSP to present antigenic peptides to the immune system, so this system can recognise the prostate tumour cells as foreign to mount an effective antitumoral response; and (iii) using treatment planning models taking into account the HSP expression levels to obtain more effective therapies. In summary, the study of the HSP during tumorigenesis as well as during cancer progression, and the inclusion of treatment designs targeting HSP combined with other treatment modalities, should improve prostate cancer survival in the near future.
热休克蛋白（HSP）构成了伴侣蛋白超家族，存在于所有细胞和所有细胞区室中，与协同/重叠的多种功能进行复杂的相互作用，尽管常见的效果是细胞保护。有几个原因解释了为什么需要在前列腺癌中研究 HSP：（1）这些分子作为肿瘤发生的伴侣发挥作用，伴随着前列腺癌细胞的出现，（2）它们作为与疾病侵袭性相关的有用分子标志物出现，并与包括激素治疗、放疗、化疗和热疗在内的抗癌治疗的耐药性相关，（3）它们可以用作治疗靶点。后一种方法可以通过以下方式实现：（i）中断 HSP（主要是 HSPC1）与各种客户蛋白的相互作用，当 HSP 对其进行伴侣时，这些客户蛋白会免受降解；（ii）利用某些 HSP 的伴侣和辅助能力将抗原肽呈递给免疫系统，以便免疫系统能够识别前列腺肿瘤细胞为外来物，从而产生有效的抗肿瘤反应；（iii）使用考虑 HSP 表达水平的治疗计划模型，以获得更有效的治疗方法。总之，研究 HSP 在肿瘤发生以及癌症进展过程中的作用，以及将针对 HSP 的治疗设计与其他治疗方式相结合，应该能够在不久的将来提高前列腺癌的生存率。
