title: Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.
abstract: Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.
authors.affiliation: Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Delitto
authors.affiliation: Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Judge
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Delitto
authors.affiliation: Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Nosacka
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: Rocha
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Bayli B
authors.initials: BB
authors.lastname: DiVita
authors.affiliation: Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gerber
authors.affiliation: Department of Medicine, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: George
authors.affiliation: Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Behrns
authors.affiliation: Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallet
authors.affiliation: Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Judge
authors.affiliation: Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Trevino
mesh_terms: D000818:Animals; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications*; D014157:Transcription Factors; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014157:Transcription Factors
keywords: cachexia; inflammation; muscle wasting; pancreatic cancer; xenografts