Cancer Research · 2006 · 490 citations · 24 references
Life SciencesImmunologyOncologyInflammationInnate ImmunitySignal TransductionCytokine BiologyCytokine SignalingInflammation-associated CarcinogenesisInflammatory SignalingInnate Immune Signaling PathwaysToll-like ReceptorsInflammation-mediated CarcinogenesisMyd88-dependent SignalingProinflammatory MediatorsToll-like Receptor SignalingToll-like Receptor Signaling PathwaysToll-like Receptor-mediated Innate Immune ResponseToll-like Receptors In CancerToll-like Receptors In Inflammation
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.
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