Department of Orthopedics, Chung Shan Medical University Hospital, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Cancer Metastasis Rev. 2020 Mar;39(1):303-320. doi: 10.1007/s10555-020-09845-2.
Melatonin is an indole produced by the pineal gland at night under normal light or dark conditions, and its levels, which are higher in children than in adults, begin to decrease prior to the onset of puberty and continue to decline thereafter. Apart from circadian regulatory actions, melatonin has significant apoptotic, angiogenic, oncostatic, and antiproliferative effects on various cancer cells. Particularly, the ability of melatonin to inhibit skeletomuscular sarcoma, which most commonly affects children, teenagers, and young adults, is substantial. In the past few decades, the vast majority of references have focused on the concept of epithelial-mesenchymal transition involvement in invasion and migration to allow carcinoma cells to dissociate from each other and to degrade the extracellular matrix. Recently, researchers have applied this idea to sarcoma cells of mesenchymal origin, e.g., osteosarcoma and Ewing sarcoma, with their ability to initiate the invasion-metastasis cascade. Similarly, interest of the effects of melatonin has shifted from carcinomas to sarcomas. Herein, in this state-of-the-art review, we compiled the knowledge related to the molecular mechanism of antimetastatic actions of melatonin on skeletomuscular sarcoma as in childhood and during adolescence. Utilization of melatonin as an adjuvant with chemotherapeutic drugs for synergy and fortification of the antimetastatic effects for the reinforcement of therapeutic actions are considered.
褪黑素是一种由松果腺在夜间产生的吲哚，无论在正常光照还是黑暗条件下，其水平在儿童中都高于成人。褪黑素水平在青春期前开始下降，并在此后继续下降。除了对昼夜节律的调节作用外，褪黑素对各种癌细胞还具有明显的凋亡、血管生成、肿瘤抑制和抗增殖作用。特别是褪黑素抑制最常见于儿童、青少年和年轻成年人的骨骼肌肉肉瘤的能力非常显著。在过去的几十年中，绝大多数参考文献都集中在涉及上皮-间充质转化的概念上，这种转化允许癌细胞彼此分离并降解细胞外基质，从而允许癌细胞侵入和迁移。最近，研究人员将这一概念应用于间充质来源的肉瘤细胞，例如骨肉瘤和尤文肉瘤，以及它们引发侵袭-转移级联的能力。同样，褪黑素的作用也从癌症转移到了肉瘤。在本文的综述中，我们汇集了与褪黑素对骨骼肌肉肉瘤的抗转移作用的分子机制相关的知识，包括儿童期和青春期的骨骼肌肉肉瘤。考虑将褪黑素作为辅助化疗药物的应用，以增强协同作用和加强抗转移效果，从而增强治疗作用。
