Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer c...

Full description

Bibliographic Details
Main Authors:	Mu, Xiaodong, Agarwal, Rashmi, March, Daniel, Rothenberg, Adam, Voigt, Clifford, Tebbets, Jessica, Huard, Johnny, Weiss, Kurt
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917717/

id	pubmed-4917717
recordtype	oai_dc
spelling	pubmed-49177172016-07-04 Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma Mu, Xiaodong Agarwal, Rashmi March, Daniel Rothenberg, Adam Voigt, Clifford Tebbets, Jessica Huard, Johnny Weiss, Kurt Research Article Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia. Hindawi Publishing Corporation 2016 2016-06-09 /pmc/articles/PMC4917717/ /pubmed/27378829 http://dx.doi.org/10.1155/2016/3758162 Text en Copyright © 2016 Xiaodong Mu et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mu, Xiaodong Agarwal, Rashmi March, Daniel Rothenberg, Adam Voigt, Clifford Tebbets, Jessica Huard, Johnny Weiss, Kurt
spellingShingle	Mu, Xiaodong Agarwal, Rashmi March, Daniel Rothenberg, Adam Voigt, Clifford Tebbets, Jessica Huard, Johnny Weiss, Kurt Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma
author_facet	Mu, Xiaodong Agarwal, Rashmi March, Daniel Rothenberg, Adam Voigt, Clifford Tebbets, Jessica Huard, Johnny Weiss, Kurt
author_sort	Mu, Xiaodong
title	Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma
title_short	Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma
title_full	Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma
title_fullStr	Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma
title_full_unstemmed	Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma
title_sort	notch signaling mediates skeletal muscle atrophy in cancer cachexia caused by osteosarcoma
description	Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.
publisher	Hindawi Publishing Corporation
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917717/
_version_	1613598406874234880

Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

Similar Items