Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Exp Biol Med (Maywood). 2021 Oct;246(19):2118-2127. doi: 10.1177/15353702211009213. Epub 2021 Apr 25.
Cancer-induced muscle wasting, i.e. cachexia, is associated with different types of cancer such as pancreatic, colorectal, lung, liver, gastric and esophageal. Cachexia affects prognosis and survival in cancer, and it is estimated that it will be the ultimate cause of death for up to 30% of cancer patients. Musculoskeletal alterations are known hallmarks of cancer cachexia, with skeletal muscle atrophy and weakness as the most studied. Recent evidence has shed light on the presence of bone loss in cachectic patients, even in the absence of bone-metastatic disease. In particular, we and others have shown that muscle and bone communicate by exchanging paracrine and endocrine factors, known as myokines and osteokines. This review will focus on describing the role of the most studied myokines, such as myostatin, irisin, the muscle metabolite β-aminoisobutyric acid, BAIBA, and IL-6, and osteokines, including TGF-β, osteocalcin, sclerostin, RANKL, PTHrP, FGF23, and the lipid mediator, PGE during cancer-induced cachexia. The interplay of muscle and bone factors, together with tumor-derived soluble factors, characterizes a complex clinical scenario in which musculoskeletal alterations are amongst the most debilitating features. Understanding and targeting the "secretome" of cachectic patients will likely represent a promising strategy to preserve bone and muscle during cancer cachexia thereby enhancing recovery.
癌症引起的肌肉消耗，即恶病质，与多种类型的癌症有关，如胰腺癌、结直肠癌、肺癌、肝癌、胃癌和食管癌。恶病质会影响癌症患者的预后和生存，据估计，多达 30%的癌症患者最终将死于恶病质。肌肉骨骼改变是恶病质的已知特征，骨骼肌萎缩和无力是研究最多的。最近的证据表明，即使没有骨转移疾病，恶病质患者也存在骨质流失。特别是，我们和其他人已经表明，肌肉和骨骼通过交换旁分泌和内分泌因子进行交流，这些因子被称为肌因子和骨因子。这篇综述将重点描述研究最多的肌因子的作用，如肌肉生长抑制素、鸢尾素、肌肉代谢物β-氨基异丁酸、BAIBA 和 IL-6，以及骨因子，包括 TGF-β、骨钙素、骨硬化蛋白、RANKL、PTHrP、FGF23 和脂类介质 PGE 在癌症引起的恶病质中的作用。肌肉和骨骼因素的相互作用，加上肿瘤衍生的可溶性因素，构成了一个复杂的临床情况，其中肌肉骨骼改变是最虚弱的特征之一。了解和靶向恶病质患者的“分泌组”可能是在癌症恶病质期间保留肌肉和骨骼从而增强恢复的有前途的策略。
