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Updated: Mar 18, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

Xiaodong Mu1, Rashmi Agarwal2, Daniel March2

  • 1Department of Orthopaedic Surgery, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA.

Sarcoma
|July 6, 2016
PubMed

Insights

Notch signaling drives muscle atrophy in cancer cachexia. Tumor-derived exosomes activate Notch in muscle stem cells, inhibiting muscle growth and worsening cachexia.

Area of Science:

  • Oncology
  • Cell Biology
  • Muscle Physiology

Background:

  • Cancer cachexia involves skeletal muscle atrophy due to tumor factors.
  • Notch signaling regulates cancer and muscle stem cell activity.
  • Its role in cancer cachexia-induced muscle atrophy is unclear.

Purpose of the Study:

  • Investigate Notch signaling's role in sarcoma-associated cachexia and muscle atrophy.
  • Determine if Notch inhibition can mitigate muscle atrophy.
  • Elucidate the mechanism of Notch signaling in tumor-muscle interactions.

Main Methods:

  • Established an orthotopic murine osteosarcoma model of cachexia.
  • Assessed Notch signaling activity in tumor and muscle tissues.
  • Evaluated the effect of systemic Notch inhibition on muscle atrophy.
  • Performed in vitro co-culture of osteosarcoma cells and muscle-derived stem cells (MDSCs).

Main Results:

  • Sarcoma-bearing mice exhibited skeletal muscle atrophy with high Notch activity in tumors and muscles.
  • Systemic Notch inhibition significantly reduced muscle atrophy.
  • Osteosarcoma cells reduced MDSC myogenic potential in vitro.
  • Notch inhibition rescued the repressed myogenic potential of MDSCs.
  • Exosomes from osteosarcoma cells contained Notch-activating factors that repressed myogenesis.

Conclusions:

  • Notch signaling is highly active in cancer cachexia and contributes to skeletal muscle atrophy.
  • Targeting Notch signaling may be a therapeutic strategy for muscle wasting in cancer.
  • Tumor-derived exosomes mediate Notch activation in muscle stem cells, impairing myogenesis.

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