@article{Doerner:2016dta,
abstract = {Obesity and related metabolic disturbances are closely associated with pathologies that represent a significant burden to global health. Epidemiological and molecular evidence links obesity and metabolic status with inflammation and increased risk of cancer. Here, using a mouse model of intestinal neoplasia and strains that are susceptible or resistant to diet-induced obesity, it is demonstrated that high-fat diet-induced inflammation, rather than obesity or metabolic status, is associated with increased intestinal neoplasia. The complement fragment C5a acts as the trigger for inflammation and intestinal tumorigenesis. High-fat diet induces complement activation and generation of C5a, which in turn induces the production of proinflammatory cytokines and expression of proto-oncogenes. Pharmacological and genetic targeting of the C5a receptor reduced both inflammation and intestinal polyposis, suggesting the use of complement inhibitors for preventing diet-induced neoplasia.
IMPLICATIONS:This study characterizes the relations between diet and metabolic conditions on risk for a common cancer and identifies complement activation as a novel target for cancer prevention. Mol Cancer Res; 14(10); 953-65. {\textcopyright}2016 AACR.},
added-at = {2017-12-08T05:18:19.000+0100},
affiliation = {Department of Genetics, Case Western Reserve University, Cleveland, Ohio.},
author = {Doerner, Stephanie K and Reis, Edimara S and Leung, Elaine S and Ko, Justine S and Heaney, Jason D and Berger, Nathan A and Lambris, John D. and Nadeau, Joseph H},
biburl = {https://www.bibsonomy.org/bibtex/2e1efcba2dd22f28e1c7d3b00daa943f9/lambris},
date-added = {2017-12-08T04:15:42GMT},
date-modified = {2017-12-08T04:17:38GMT},
doi = {10.1158/1541-7786.MCR-16-0153},
interhash = {9fb6f3bd8972449080bd14f70825af95},
intrahash = {e1efcba2dd22f28e1c7d3b00daa943f9},
journal = {Molecular cancer research : MCR},
keywords = {imported},
language = {English},
month = oct,
number = 10,
pages = {953--965},
pmcid = {PMC5330314},
pmid = {27535705},
rating = {0},
timestamp = {2017-12-08T05:18:19.000+0100},
title = {{High-Fat Diet-Induced Complement Activation Mediates Intestinal Inflammation and Neoplasia, Independent of Obesity.}},
uri = {\url{papers3://publication/doi/10.1158/1541-7786.MCR-16-0153}},
url = {http://mcr.aacrjournals.org/cgi/doi/10.1158/1541-7786.MCR-16-0153},
volume = 14,
year = 2016
}