TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jul 15

PMID 26172047

Citations 51

Authors

Stephanie H Greco

Lena Tomkotter

Anne-Kristin Vahle

Rae Rokosh

Antonina Avanzi

Syed Kashif Mahmood

Michael Deutsch

Sara Alothman

Dalia Alqunaibit

Atsuo Ochi

Constantinos Zambirinis

Tasnima Mohaimin

Mauricio Rendon

Elliot Levie

Mridul Pansari

Alejandro Torres-Hernandez

Donnele Daley

Rocky Barilla

H Leon Pachter

Daniel Tippens

Hassan Malik

Allal Boutajangout

Thomas Wisniewski

George Miller

Affiliations

Soon will be listed here.

Abstract

Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

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