TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer
TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer
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DOI：
10.1158/0008-5472.can-05-3948
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Mor, G
中科院分区：
文献类型：
--
作者：
Kelly, MG;Alvero, AB;Mor, G
有证据表明，在特定部位持续存在的细胞因子和趋化因子的炎症谱会导致慢性疾病的发展。最近的研究表明，细菌感染可能是炎症和癌变之间的一个联系；然而，所涉及的关键分子途径仍然未知。我们假设一个可能导致癌变炎症的上游信号通路可能由toll样受体（TLR）介导。我们首次描述了卵巢癌细胞获得的一种适应性机制，使它们能够促进促炎环境并产生化疗耐药性。我们认为TLR-4-MyD88信号通路可能是癌症发生的危险因素，并可能代表生物调节剂开发的新靶点。我们的工作解释了细菌产物，如脂多糖，是如何直接从肿瘤中促进促炎细胞因子的产生和提高肿瘤存活率的。此外，我们还提供了新的证据，证明TLR-4信号通路与卵巢癌细胞的炎症和化疗耐药有关。
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.