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[Cancer Research 66, 3859-3868, April 1, 2006]
© 2006 American Association for Cancer Research


Immunology

TLR-4 Signaling Promotes Tumor Growth and Paclitaxel Chemoresistance in Ovarian Cancer

Michael G. Kelly, Ayesha B. Alvero, Rui Chen, Dan-Arin Silasi, Vikki M. Abrahams, Serena Chan, Irene Visintin, Thomas Rutherford and Gil Mor

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Requests for reprints: Gil Mor, Department of Obstetrics, Gynecology, and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar Street, FMB 301, New Haven, CT 06520. Phone: 203-785-6294; Fax: 203-785-4883; E-mail: gil.mor{at}yale.edu.

Evidence suggests that an inflammatory profile of cytokines and chemokines persisting at a particular site would lead to the development of a chronic disease. Recent studies implicate bacterial infection as one possible link between inflammation and carcinogenesis; however, the crucial molecular pathways involved remain unknown. We hypothesized that one possible upstream signaling pathway leading to inflammation in carcinogenesis may be mediated by Toll-like receptors (TLR). We describe for the first time an adaptive mechanism acquired by ovarian cancer cells that allows them to promote a proinflammatory environment and develop chemoresistance. We propose that the TLR-4-MyD88 signaling pathway may be a risk factor for developing cancer and may represent a novel target for the development of biomodulators. Our work explains how bacterial products, such as lipopolysaccharide, can promote, directly from the tumor, the production of proinflammatory cytokines and the enhancement of tumor survival. In addition, we provide new evidence that links TLR-4 signaling, inflammation, and chemoresistance in ovarian cancer cells. (Cancer Res 2006; 66(7): 3859-68)




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.