Department of Anatomy & Physiology, Centre for Muscle Research, University of Melbourne, Parkville, Australia.
Division of Rehabilitation Sciences, University of Tennessee Health Science Center, Memphis, Tennessee.
Am J Physiol Cell Physiol. 2022 Aug 1;323(2):C378-C384. doi: 10.1152/ajpcell.00021.2022. Epub 2022 Jun 15.
Skeletal muscle atrophy and dysfunction contribute to morbidity and mortality in patients with cancer. Cachexia pathophysiology is highly complex, given that perturbations to the systemic cancer environment and the interaction with diverse tissues can contribute to wasting processes. Systemic interleukin 6 (IL-6) and glycoprotein 130 (gp130) receptors signaling have established roles in some types of cancer-induced muscle wasting through disruptions to protein turnover and oxidative capacity. Although exercise has documented benefits for cancer prevention and patient survival, there are significant gaps in our understanding of muscle adaptation and plasticity during severe cachexia. Preclinical models have provided valuable insight into the adaptive potential of muscle contraction within the cancer environment. We summarize the current understanding of how resistance-type exercise impacts mechanisms involved in cancer-induced muscle atrophy and dysfunction. Specifically, the role of IL-6 and gp130 receptors in the pathophysiology of muscle wasting and the adaptive response to exercise is explained. The discussion includes current knowledge gaps and future research directions needed to improve preclinical research and accelerate clinical translation in human patients with cancer.
骨骼肌萎缩和功能障碍导致癌症患者的发病率和死亡率升高。恶病质的病理生理学非常复杂，因为全身性癌症环境的改变以及与多种组织的相互作用都会导致消耗过程。全身性白细胞介素 6（IL-6）和糖蛋白 130（gp130）受体信号在某些类型的癌症引起的肌肉消耗中起着重要作用，这是通过破坏蛋白质周转率和氧化能力实现的。尽管运动对癌症预防和患者生存有明确的益处，但我们对严重恶病质期间肌肉适应和可塑性的理解仍存在重大差距。临床前模型为我们了解肌肉在癌症环境下的收缩适应性提供了宝贵的见解。我们总结了目前对抵抗型运动如何影响癌症引起的肌肉萎缩和功能障碍相关机制的理解。具体来说，解释了 IL-6 和 gp130 受体在肌肉消耗的病理生理学以及对运动的适应性反应中的作用。讨论包括当前的知识空白和未来需要进行的研究方向，以改善临床前研究并加速癌症患者的临床转化。
