Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kir, S; White, JP; Kleiner, S; Kazak, L; Cohen, P; Baracos, VE; Spiegelman, BM

Published Date

  • September 2014

Published In

Volume / Issue

  • 513 / 7516

Start / End Page

  • 100 - 104

PubMed ID

  • 25043053

Pubmed Central ID

  • 25043053

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature13528

Language

  • eng