Mathematical Model of Muscle Wasting in Cancer Cachexia

Author:

Farhang-Sardroodi SuzanORCID,Wilkie Kathleen P.ORCID

Abstract

Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass which negatively impacts patient’s quality of life, reduces their ability to sustain anticancer therapies, and increases the risk of mortality. Recent discoveries have identified the myostatin/activin-ActRIIB pathway as critical to muscle wasting by inducing satellite cell quiescence and increasing muscle-specific ubiquitin ligases responsible for atrophy. Remarkably, pharmacological blockade of the ActRIIB pathway has shown to reverse muscle wasting and prolong the survival time of tumor-bearing animals. To explore the implications of this signaling pathway and potential therapeutic targets in cachexia, we construct a novel mathematical model of muscle tissue subjected to tumor-derived cachexic factors. The model formulation tracks the intercellular interactions between cancer, satellite cell, and muscle cell populations. The model is parameterized by fitting to colon-26 mouse model data, and analysis provides insight into tissue growth in healthy, cancerous, and post-treatment conditions. Model predictions suggest that cachexia fundamentally alters muscle tissue health, as measured by the stem cell ratio, and this is only partially recovered by anti-cachexia treatment. Our mathematical findings suggest that the activation and proliferation of satellite cells, after blocking the myostatin/activin B pathway, is required to partially recover cancer-induced muscle loss.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3