Dataset Information

Mechanisms associated with systemic effects of cancer

ABSTRACT: Cancer is considered as a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of cancer can lead to weakness in muscles and heart, which hastens cancer-associated death. The majority of preclinical studies, including our own, on cancer-induced skeletal muscle defects utilized mouse models and C2C12 myoblast cell line of mouse origin (>7,700 publications). However, a recent study reported distinct metabolic pathways in mouse compared to human. For example, while higher fasting circulating levels of glucose in human is associated with shortened lifespan, it is associated with longer lifespan in mouse. Since the metabolic activity of the skeletal muscle primarily determines circulating glucose levels, skeletal muscle in mouse and human may function differently and not all skeletal muscle defects noted in tumor-bearing mice may not translate into human. Therefore, we developed a robust human model system using human muscle stem cells to understand cancer-induced skeletal muscle defects in human. We found conditioned media from breast cancer cell lines affected cell molecular biomarkers (e.g. PAX7 annd MyOD) and cell surface markers (e.g. CD82, CD54 and CD90) which were associated with dynamic changes of mRNAs, proteins and peptides in human muscle stem cells or human myotubes differentiated from human muscle stem cells. This study will help in cost-effective discovery of drugs that are effective irrespective genetic ancestry and reveal utility of two class of drugs to overcome cancer-induced skeletal muscle defects

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skeletal Muscle

SUBMITTER: Emma Doud

LAB HEAD: Amber Mosley

PROVIDER: PXD034000 | Pride | 2023-05-10

REPOSITORIES: Pride

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			Action	DRS
	2020_05_32_Nakshatri_Reggie_Global4plexwithTMTpro_Exploris180minNoFAIMS_TMTturbo_F1.raw	Raw
	2020_05_32_Nakshatri_Reggie_Global4plexwithTMTpro_Exploris180minNoFAIMS_TMTturbo_F2.raw	Raw
	2020_05_32_Nakshatri_Reggie_Global4plexwithTMTpro_Exploris180minNoFAIMS_TMTturbo_F3.raw	Raw
	2020_05_32_Nakshatri_Reggie_Global4plexwithTMTpro_Exploris180minNoFAIMS_TMTturbo_F4.raw	Raw
	2020_05_32_Nakshatri_Reggie_Global4plexwithTMTpro_Exploris180minNoFAIMS_TMTturbo_F5.raw	Raw

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Publications

A human skeletal muscle stem/myotube model reveals multiple signaling targets of cancer secretome in skeletal muscle.

Wang Ruizhong R Kumar Brijesh B Bhat-Nakshatri Poornima P Khatpe Aditi S AS Murphy Michael P MP Wanczyk Kristen E KE Simpson Edward E Chen Duojiao D Gao Hongyu H Liu Yunlong Y Doud Emma H EH Mosley Amber L AL Nakshatri Harikrishna H

iScience 20230331 4

Skeletal muscle dysfunction or reprogramming due to the effects of the cancer secretome is observed in multiple malignancies. Although mouse models are routinely used to study skeletal muscle defects in cancer, because of species specificity of certain cytokines/chemokines in the secretome, a human model system is required. Here, we establish simplified multiple skeletal muscle stem cell lines (hMuSCs), which can be differentiated into myotubes. Using single nuclei ATAC-seq (snATAC-seq) and RNA- ...[more]

PMID: 37102148

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