@article{82d41772d926444f8ace980e1f0c3ec0,
title = "STAT3 in epithelial cells regulates inflammation and tumor progression to malignant state in colon",
abstract = "Chronic inflammation is an important risk factor for the development of colorectal cancer; however, the mechanism of tumorigenesis especially tumor progression to malignancy in the inflamed colon is still unclear. Our study shows that epithelial signal transducer and activator of transcription 3 (STAT3), persistently activated in inflamed colon, is not required for inflammation-induced epithelial overproliferation and the development of early-stage tumors; however, it is essential for tumor progression to advanced malignancy. We found that one of the mechanisms that epithelial STAT3 regulates in tumor progression might be to modify leukocytic infiltration in the large intestine. Activation of epithelial STAT3 promotes the infiltration of the CD8+ lymphocyte population but inhibits the recruitment of regulatory T (Treg) lymphocytes. The loss of Stat3 in epithelial cells promoted the expression of cytokines/chemokines including CCL19, CCL28, and RANTES, which are known to be able to recruit Treg lymphocytes. Linked to these changes was the pathway mediated by sphingosine 1-phosphate receptor 1 and sphingosine 1-phosphate kinases, which is activated in colonic epithelial cells in inflamed colon with functional STAT3 but not in epithelial cells deleted of STAT3. Our data suggest that epithelial STAT3 plays a critical role in inflammation-induced tumor progression through regulation of leukocytic recruitment especially the infiltration of Treg cells in the large intestine.",
author = "Nguyen, {Andrew V.} and Wu, {Yuan Yuan} and Qiang Liu and Donghai Wang and Stephanie Nguyen and Ricky Loh and Joey Pang and Kenneth Friedman and Amos Orlofsky and Leonard Augenlicht and Pollard, {Jeffrey W.} and Lin, {Elaine Y.}",
note = "Funding Information: Abbreviations: DSS, dextran sodium sulfate; S1P, sphingosine 1-phosphate; S1PR1, sphingosine 1-phosphate receptor 1; STAT3, signal transducer and activator of transcription 3; Stat3flox/flox mice, control mice with floxed P sites in the introns of Stat3 gene; Stat3-EIKO, conditional knockout mice with Stat3 deletion in hematopoietic and intestinal epithelial cells; Stat3-IKO, conditional knockout mice with Stat3 deletion in hematopoietic cells; Stat3-VKO, conditional knockout mice with Stat3 deletion in intestinal epithelial cells Address all correspondence to: Andrew V. Nguyen, PhD, 222 56th Avenue, Room 202, Medical Arts Building, Bayside, NY 11364. E-mail: anguyen@qcc.cuny.edu or Elaine Y. Lin, MD, PhD, Department of Medicine, Albert Einstein Cancer Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. E-mail: ELIN@montefiore.org 1This work was supported in part by Montefiore Medical Center New Research Initiative Award, Miriam Mandel Faculty Scholar Award, the Albert Einstein Cancer Center Core grant P30 CA13330, Montefiore Medical Center Pathology Department Faculty Research Fund, and Professional Staff Congress of the City University of New York to A.V.N. The authors declare no competing financial interests and no conflict of interests between the authors and reviewers. 2These authors contributed equally to this work. Received 9 May 2013; Revised 26 June 2013; Accepted 2 July 2013 Copyright {\textcopyright} 2013 Neoplasia Press, Inc. All rights reserved 1522-8002/13/$25.00 DOI 10.1593/neo.13952",
year = "2013",
month = sep,
doi = "10.1593/neo.13952",
language = "English (US)",
volume = "15",
pages = "998--1008",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "9",
}
