| Autor: |
Lu, Feiqi, Osei-Hwedieh, David, Mandell, Jonathan B, Morales-Restrepo, Alejandro, Hankins, Margaret L, Crasto, Jared A, Ma, Ruichen, Dinh, Vu, Watters, Rebecca J, Weiss, Kurt R |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Popis: |
Cancer-associated cachexia is a wasting syndrome that affects up to 50% of cancer patients. It is defined as unintentional weight loss ≥5% over 6 months and characterized by muscle atrophy, fatigue, and anorexia that are refractory to nutritional support. Sarcoma describes a diverse group of malignancies arising from the connective tissues. Sarcoma patients are uniquely susceptible to cancer-associated cachexia given its origins in the musculoskeletal system. Our previous research suggests that sarcoma cells may contribute to sarcoma-associated cachexia (SAC) via establishment of TNF-α-mediated inflammation and dysregulation of muscle homeostasis by abnormal Notch signaling. Here, we examine the role of the Notch pathway and pro-inflammatory cytokines in cells derived from cachectic and non-cachectic human sarcoma patients. We observed increased expression of Notch pathway genes in the cachexia group while no differences in pro-inflammatory cytokines were observed. Co-culture of muscle-derived stem cells (MDSCs) and sarcoma cells demonstrated the inhibition of MDSC maturation with both cachectic and non-cachectic patient cells, corresponding to elevated Pax7 and Notch pathway expression in MDSCs. Our findings suggest that there is no difference in inflammatory profile between cachexia and non-cachexia sarcoma samples. However, Cachectic sarcoma samples express increased Notch that mediates muscle wasting possibly through inhibition of myogenesis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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