Detection of pancreatic cancer-induced cachexia using a fluorescent myoblast reporter system and analysis of metabolite abundance

Paul T. Winnard, Santosh K. Bharti, Marie France Penet, Radharani Marik, Yelena Mironchik, Flonne Wildes, Anirban Maitra, Zaver M. Bhujwalla

Research output: Contribution to journalArticle

Abstract

The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm3. Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development.

LanguageEnglish (US)
Pages1441-1450
Number of pages10
JournalCancer Research
Volume76
Issue number6
DOIs
StatePublished - Mar 15 2016

Fingerprint

Cachexia
Myoblasts
Systems Analysis
Pancreatic Neoplasms
Weight Loss
Tumor Burden
Neoplasms
Optical Devices
Molecular Imaging
Optical Imaging
Valine
Therapeutics
Heterografts
Alanine
Skeletal Muscle
Adenocarcinoma
Survival Rate
Biomarkers
Cholesterol
Transplants

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Detection of pancreatic cancer-induced cachexia using a fluorescent myoblast reporter system and analysis of metabolite abundance. / Winnard, Paul T.; Bharti, Santosh K.; Penet, Marie France; Marik, Radharani; Mironchik, Yelena; Wildes, Flonne; Maitra, Anirban; Bhujwalla, Zaver M.

In: Cancer Research, Vol. 76, No. 6, 15.03.2016, p. 1441-1450.

Research output: Contribution to journalArticle

@article{6ffe12c39bcd4c01ae29006df4fd6c30,
title = "Detection of pancreatic cancer-induced cachexia using a fluorescent myoblast reporter system and analysis of metabolite abundance",
abstract = "The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body {"}holistic{"} approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2{\%} to 2.7{\%} and tumor burdens of only approximately 79 to 170 mm3. Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development.",
author = "Winnard, {Paul T.} and Bharti, {Santosh K.} and Penet, {Marie France} and Radharani Marik and Yelena Mironchik and Flonne Wildes and Anirban Maitra and Bhujwalla, {Zaver M.}",
year = "2016",
month = "3",
day = "15",
doi = "10.1158/0008-5472.CAN-15-1740",
language = "English (US)",
volume = "76",
pages = "1441--1450",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - Detection of pancreatic cancer-induced cachexia using a fluorescent myoblast reporter system and analysis of metabolite abundance

AU - Winnard,Paul T.

AU - Bharti,Santosh K.

AU - Penet,Marie France

AU - Marik,Radharani

AU - Mironchik,Yelena

AU - Wildes,Flonne

AU - Maitra,Anirban

AU - Bhujwalla,Zaver M.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm3. Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development.

AB - The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm3. Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development.

UR - http://www.scopus.com/inward/record.url?scp=84962124796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962124796&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-15-1740

DO - 10.1158/0008-5472.CAN-15-1740

M3 - Article

VL - 76

SP - 1441

EP - 1450

JO - Journal of Cancer Research

T2 - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 6

ER -