Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Human Anatomy and Histology, University of Palermo, Via del Vespro, 127, Palermo, PA, 90129, Italy.
Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD, USA.
J Mol Histol. 2023 Apr;54(2):105-118. doi: 10.1007/s10735-023-10119-8. Epub 2023 Mar 18.
The chaperone system (CS) of an organism is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone receptors and interactors. It is present throughout the body but with distinctive features for each cell and tissue type. Previous studies pertaining to the CS of the salivary glands have determined the quantitative and distribution patterns for several members, the chaperones, in normal and diseased glands, focusing on tumors. Chaperones are cytoprotective, but can also be etiopathogenic agents causing diseases, the chaperonopathies. Some chaperones such as Hsp90 potentiate tumor growth, proliferation, and metastasization. Quantitative data available on this chaperone in salivary gland tissue with inflammation, and benign and malignant tumors suggest that assessing tissue Hsp90 levels and distribution patterns is useful for differential diagnosis-prognostication, and patient follow up. This, in turn, will reveal clues for developing specific treatment centered on the chaperone, for instance by inhibiting its pro-carcinogenic functions (negative chaperonotherapy). Here, we review data on the carcinogenic mechanisms of Hsp90 and their inhibitors. Hsp90 is the master regulator of the PI3K-Akt-NF-kB axis that promotes tumor cell proliferation and metastasization. We discuss pathways and interactions involving these molecular complexes in tumorigenesis and review Hsp90 inhibitors that have been tested in search of an efficacious anti-cancer agent. This targeted therapy deserves extensive investigation in view of its theoretical potential and some positive practical results and considering the need of novel treatments for tumors of the salivary glands as well as other tissues.
机体的伴侣系统 (CS) 由分子伴侣、伴侣辅助因子、共伴侣、伴侣受体和相互作用蛋白组成。它存在于全身，但每种细胞和组织类型都有其独特的特征。以前有关唾液腺 CS 的研究确定了几种伴侣在正常和患病（重点是肿瘤）腺体中的定量和分布模式。伴侣具有细胞保护作用，但也可能是引起疾病（伴侣病）的病因。一些伴侣，如 Hsp90，可增强肿瘤的生长、增殖和转移。有关唾液腺组织中炎症、良性和恶性肿瘤的这种伴侣的定量数据表明，评估组织 Hsp90 水平和分布模式对于鉴别诊断-预后和患者随访很有用。这反过来又会为开发以伴侣为中心的特定治疗方法提供线索，例如通过抑制其致癌功能（负伴侣治疗）。在这里，我们综述了 Hsp90 的致癌机制及其抑制剂的数据。Hsp90 是促进肿瘤细胞增殖和转移的 PI3K-Akt-NF-kB 轴的主要调节剂。我们讨论了这些分子复合物在肿瘤发生中的途径和相互作用，并综述了已在研究中测试的 Hsp90 抑制剂，以寻找有效的抗癌药物。鉴于其理论潜力和一些积极的实际结果，以及对唾液腺肿瘤以及其他组织的新型治疗方法的需求，这种靶向治疗值得广泛研究。
