Cancer cachexia is a devastating syndrome occurring in the majority of terminally ill cancer patients. Notably, skeletal muscle atrophy is a consistent feature affecting the quality of life and prognosis. To date, limited therapeutic options are available, and research in the field is hampered by the lack of satisfactory models to study the complexity of wasting in cachexia-inducing tumors, such as pancreatic cancer. Moreover, currently used in vivo models are characterized by an explosive cachexia with a lethal wasting within few days, while pancreatic cancer patients might experience alterations long before the onset of overt wasting. In this work, we established and characterized a slow-paced model of pancreatic cancer-induced muscle wasting that promotes efficient muscular wasting in vitro and in vivo. Treatment with conditioned media from pancreatic cancer cells led to the induction of atrophy in vitro, while tumor-bearing mice presented a clear reduction in muscle mass and functionality. Intriguingly, several metabolic alterations in tumor-bearing mice were identified, paving the way for therapeutic interventions with drugs targeting metabolism.

Metabolic Alterations in a Slow-Paced Model of Pancreatic Cancer-Induced Wasting.

Reano
Secondo
;
Filigheddu N;
2018-01-01

Abstract

Cancer cachexia is a devastating syndrome occurring in the majority of terminally ill cancer patients. Notably, skeletal muscle atrophy is a consistent feature affecting the quality of life and prognosis. To date, limited therapeutic options are available, and research in the field is hampered by the lack of satisfactory models to study the complexity of wasting in cachexia-inducing tumors, such as pancreatic cancer. Moreover, currently used in vivo models are characterized by an explosive cachexia with a lethal wasting within few days, while pancreatic cancer patients might experience alterations long before the onset of overt wasting. In this work, we established and characterized a slow-paced model of pancreatic cancer-induced muscle wasting that promotes efficient muscular wasting in vitro and in vivo. Treatment with conditioned media from pancreatic cancer cells led to the induction of atrophy in vitro, while tumor-bearing mice presented a clear reduction in muscle mass and functionality. Intriguingly, several metabolic alterations in tumor-bearing mice were identified, paving the way for therapeutic interventions with drugs targeting metabolism.
File in questo prodotto:
File Dimensione Formato  
Wyart Oxydative Medicine and Cellular Longevity 2018.pdf

file ad accesso aperto

Tipologia: Documento in Pre-print
Licenza: Creative commons
Dimensione 19.85 MB
Formato Adobe PDF
19.85 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/96348
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 17
social impact