Altered exocrine function can drive adipose wasting in early pancreatic cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-06-20

AUTHORS

Laura V. Danai, Ana Babic, Michael H. Rosenthal, Emily A. Dennstedt, Alexander Muir, Evan C. Lien, Jared R. Mayers, Karen Tai, Allison N. Lau, Paul Jones-Sali, Carla M. Prado, Gloria M. Petersen, Naoki Takahashi, Motokazu Sugimoto, Jen Jen Yeh, Nicole Lopez, Nabeel Bardeesy, Carlos Fernandez-del Castillo, Andrew S. Liss, Albert C. Koong, Justin Bui, Chen Yuan, Marisa W. Welch, Lauren K. Brais, Matthew H. Kulke, Courtney Dennis, Clary B. Clish, Brian M. Wolpin, Matthew G. Vander Heiden

ABSTRACT

Malignancy is accompanied by changes in the metabolism of both cells and the organism1,2. Pancreatic ductal adenocarcinoma (PDAC) is associated with wasting of peripheral tissues, a metabolic syndrome that lowers quality of life and has been proposed to decrease survival of patients with cancer3,4. Tissue wasting is a multifactorial disease and targeting specific circulating factors to reverse this syndrome has been mostly ineffective in the clinic5,6. Here we show that loss of both adipose and muscle tissue occurs early in the development of pancreatic cancer. Using mouse models of PDAC, we show that tumour growth in the pancreas but not in other sites leads to adipose tissue wasting, suggesting that tumour growth within the pancreatic environment contributes to this wasting phenotype. We find that decreased exocrine pancreatic function is a driver of adipose tissue loss and that replacement of pancreatic enzymes attenuates PDAC-associated wasting of peripheral tissues. Paradoxically, reversal of adipose tissue loss impairs survival in mice with PDAC. When analysing patients with PDAC, we find that depletion of adipose and skeletal muscle tissues at the time of diagnosis is common, but is not associated with worse survival. Taken together, these results provide an explanation for wasting of adipose tissue in early PDAC and suggest that early loss of peripheral tissue associated with pancreatic cancer may not impair survival. More... »

PAGES

600-604

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41586-018-0235-7

DOI

http://dx.doi.org/10.1038/s41586-018-0235-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1104915639

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29925948


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