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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adipose Tissue / pathology
-
Animals
-
Cachexia / etiology
-
Cell Differentiation
-
Cell Line, Tumor
-
Cell Proliferation
-
Chemokines / metabolism
-
Cobra Cardiotoxin Proteins / pharmacology
-
Colonic Neoplasms / pathology*
-
Crotoxin / pharmacology
-
Disease Models, Animal
-
Down-Regulation
-
Drug Combinations
-
Mice
-
Muscle, Skeletal / drug effects
-
Muscle, Skeletal / pathology
-
Muscle, Skeletal / physiology*
-
Neutrophil Infiltration
-
Regeneration* / drug effects
-
Stem Cells / cytology
-
Stem Cells / metabolism
-
Transplantation, Heterologous
Substances
-
Chemokines
-
Cobra Cardiotoxin Proteins
-
Drug Combinations
-
cardiotoxin, crotoxin drug combination
-
Crotoxin
Grants and funding
This work was supported by AMED under Grant Number 18am0101084j0002 to KT, Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP to SF, Grant-in-Aid for Scientific Research (B) to SF, and Kyowa Hakko Kirin Co., Ltd. The commercial affiliation (Kyowa Hakko Kirin Co., Ltd. and Kyowa Kirin Pharmaceutical Research, Inc.) provided support in 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 specific roles of A.H. are articulated in the ‘author contributions’ section. The other funders also had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.