Journal article
Modeling Human Cancer-induced Cachexia
Cell reports (Cambridge), Vol.28(6), pp.1612-1622.e4
08/06/2019
DOI: 10.1016/j.celrep.2019.07.016
PMCID: PMC6733019
PMID: 31390573
Abstract
Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.
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•Development of a mouse model of pancreatic adenocarcinoma (PDA)-induced cachexia•Model develops progressive wasting associated with advancing pancreas pathology•Induction of cachexia in adult KPP mice models tissue loss in PDA cancer patients•Gene ontology of cachectic muscles from KPP mice resembles that of PDA patients
Talbert et al. developed an inducible mouse model of cachexia caused by pancreatic cancer. This model exhibits features of the human condition, including the progressive depletion of muscle and adipose tissue associated with tumor progression.
Details
- Title: Subtitle
- Modeling Human Cancer-induced Cachexia
- Creators
- Erin E Talbert - Medical University of South CarolinaMaria C Cuitiño - Medical University of South CarolinaKatherine J Ladner - The Ohio State UniversityPriyani V Rajasekerea - The Ohio State UniversityMelissa Siebert - The Ohio State UniversityReena Shakya - The Ohio State UniversityGustavo W Leone - Medical University of South CarolinaMichael C Ostrowski - The Ohio State UniversityBrian Paleo - The Ohio State UniversityNoah Weisleder - The Ohio State UniversityPeter J Reiser - The Ohio State UniversityAmy Webb - The Ohio State UniversityCynthia D Timmers - Medical University of South CarolinaDaniel S Eiferman - The Ohio State UniversityDavid C Evans - The Ohio State UniversityMary E Dillhoff - The Ohio State UniversityCarl R Schmidt - The Ohio State UniversityDenis C Guttridge - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.28(6), pp.1612-1622.e4
- DOI
- 10.1016/j.celrep.2019.07.016
- PMID
- 31390573
- PMCID
- PMC6733019
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: R21AR071021, R01CA180057, K99AR071508; DOI: 10.13039/100000048, name: American Cancer Society, award: PF-15-156-01-CSM; name: Weiss; name: The Ohio State Comprehensive Cancer Center, award: P30CA016058; name: OSUCCC; name: Hollings Cancer Center, award: P30CA138313; DOI: 10.13039/100000002, name: NIH, award: C06 RR015455
- Language
- English
- Date published
- 08/06/2019
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984259392802771
Metrics
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