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Toll-like receptor expression in normal ovary and ovarian tumors

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Abstract

Recent studies have implicated inflammation in the initiation and progression of ovarian cancer, though the mechanisms underlying this effect are still not clear. Toll-like receptors (TLRs) allow immune cells to recognize pathogens and to trigger inflammatory responses. Tumor cell expression of TLRs can promote inflammation and cell survival in the tumor microenvironment. Here we sought to characterize the expression of TLRs in normal human ovaries, benign and malignant ovarian tumors from patients, and in established ovarian tumor cell lines. We report that TLR2, TLR3, TLR4, and TLR5 are strongly expressed on the surface epithelium of normal ovaries. In contrast to previous studies of uterus and endocervix, we found no cyclic variation in TLR expression occurred in murine ovaries. TLR2, TLR3, TLR4, and TLR5 are expressed in benign conditions, epithelial tumors, and in ovarian cancer cell lines. Variable expression of TLR6 and TLR8 was seen in benign and malignant epithelium of some patients, while expression of TLR1, TLR7, and TLR9 was weak. Normal and malignant ovarian stroma were negative for TLR expression. Vascular endothelial cells, macrophages, and occasional fibroblasts in tumors were positive. Functional activity for TLRs was demonstrated by stimulation of cell lines with specific ligands and subsequent activation and translocation of NFκB and release of the proinflammatory cytokines interleukin-6 and CCL-2. These studies demonstrate expression of multiple TLRs in the epithelium of normal ovaries and in ovarian tumor cells, and may indicate a mechanism by which epithelial tumors manipulate inflammatory pathways to facilitate tumor progression.

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Acknowledgments

We gratefully acknowledge the expert assistance of Glenn Doerman and Maryellen Daston with graphics and editing of the manuscript, respectively. The 3EconAluc plasmid was kindly provided by Dr. Diaz-Meco, University of Cincinnati. This study was supported by a pilot project grant from the University of Cincinnati Cancer Center (AFD) and RSG-0614101CSM from the American Cancer Society (AFD).

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Authors and Affiliations

  1. Department of Cancer and Cell Biology, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH, 45267-0521, USA

    Mingfu Zhou, Molly M. McFarland-Mancini, Holly M. Funk & Angela F. Drew

  2. Division of Gynecologic Oncology, University of Cincinnati, Cincinnati, OH, USA

    Nader Husseinzadeh

  3. Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA

    Taofic Mounajjed

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  1. Mingfu Zhou
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  2. Molly M. McFarland-Mancini
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  3. Holly M. Funk
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  5. Taofic Mounajjed
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  6. Angela F. Drew
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Correspondence to Angela F. Drew.

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Zhou, M., McFarland-Mancini, M.M., Funk, H.M. et al. Toll-like receptor expression in normal ovary and ovarian tumors. Cancer Immunol Immunother 58, 1375–1385 (2009). https://doi.org/10.1007/s00262-008-0650-y

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