title: Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.
abstract: Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat. How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Serkan
authors.initials: S
authors.lastname: Kir
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: White
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleiner
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kazak
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Department of Oncology, Division of Palliative Care Medicine, University of Alberta, Edmonton T6G 1Z2, Canada.
authors.forename: Vickie E
authors.initials: VE
authors.lastname: Baracos
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002100:Cachexia / Q000378:metabolism* / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D044162:Parathyroid Hormone-Related Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D044162:Parathyroid Hormone-Related Protein