TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer

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 pat...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-04, Vol.66 (7), p.3859-3868
Main Authors: KELLY, Michael G, ALVERO, Ayesha B, RUI CHEN, SILASI, Dan-Arin, ABRAHAMS, Vikki M, CHAN, Serena, VISINTIN, Irene, RUTHERFORD, Thomas, MOR, Gil
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - biosynthesis
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - immunology
Adaptor Proteins, Signal Transducing - metabolism
Antineoplastic agents
Biological and medical sciences
Caspase 3
Caspase 9
Caspases - biosynthesis
Cell Growth Processes - drug effects
Cell Line, Tumor
Cytokines - biosynthesis
Disease-Free Survival
Drug Resistance, Neoplasm
Female
Female genital diseases
Gynecology. Andrology. Obstetrics
Humans
Interleukin-6 - biosynthesis
Lipopolysaccharides - pharmacology
Medical sciences
Myeloid Differentiation Factor 88
NF-kappa B - metabolism
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - immunology
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Paclitaxel - pharmacology
Pharmacology. Drug treatments
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Signal Transduction - physiology
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - immunology
Toll-Like Receptor 4 - metabolism
Transfection
Tumors
X-Linked Inhibitor of Apoptosis Protein - biosynthesis
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-05-3948