Muscle regeneration is disrupted by cancer cachexia without loss of muscle stem cell potential.

Shoya Inaba,Masashi Tachibana,Atsushi Hinohara,So-Ichiro Fukada,Kazutake Tsujikawa,Atsushi Asakura

doi:10.1371/journal.pone.0205467

Shoya Inaba, Masashi Tachibana + Show 4 more

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https://doi.org/10.1371/journal.pone.0205467

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Abstract

Cancer cachexia is a severe, debilitating condition characterized by progressive body wasting associated with remarkable loss of skeletal muscle weight. It has been reported that cancer cachexia disturbs the regenerative ability of skeletal muscle, but the cellular mechanisms are still unknown. Here, we investigated the skeletal muscle regenerative process in mouse colon-26 (C26) tumor cell-bearing mice as a C26 cancer cachexia model. Although the proliferation and differentiation abilities of muscle stem cells derived from the C26 tumor cell-bearing mice were sustained in vitro, the proliferation and differentiation were severely impaired in the cachexic mice. The numbers of both macrophages and mesenchymal progenitors, which are critical players in muscle regeneration, were reduced in the cancer cachexic mice, indicating that the skeletal muscle regeneration process was disrupted by cancer cachexia. Furthermore, the number of infiltrated neutrophils was also reduced in cancer cachexia mice 24 hours after muscle injury, and the expression of critical chemokines for muscle regeneration was reduced in cancer cachexia model mice compared to control mice. Collectively, although the ability to regeneration of MuSCs was retained, cancer cachexia disturbed skeletal muscle regenerative ability by inhibiting the orchestrated muscle regeneration processes.

Highlights

Cancer cachexia is considered to be a complex syndrome that affects a patient’s life expectancy [1, 2]
Our results show that the expression of critical chemokines for muscle regeneration was reduced in a cancer cachexia model mouse compared to control mice
Like a previous report [17], the weights of fat tissue were dramatically reduced only in C26-implanted mice (Fig 1D). These results indicated that these models allow us to compare muscle regenerative ability in two tumor-bearing mouse models with or without cachexia phenotypes

Summary

Introduction

Cancer cachexia is considered to be a complex syndrome that affects a patient’s life expectancy [1, 2]. The common and important characteristic of cancer cachexia is the loss of skeletal muscle that leads to pronounced body weight loss. It is considered that the wasting muscle condition affects the patient’s survival rate; the mechanisms underlying cachexia should be better understood in order to treat those patients. Muscle regeneration and cancer cachexia the form of salaries for author [A.H.], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Conclusion