Toll-like receptor expression in normal ovary and ovarian tumors

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 NFkappaB 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.

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

“…These cancerous TLRs are believed to promote both tumor growth and immune evasion through upregulation of NFκB and production of anti-apoptotic molecules [29,60,61]. A variety of cancer cells and cancer cell lines have been shown to express functionally active TLRs, such as TLR-2, -3, -4, and -5 in ovarian cancer [29,61,62], TLR-3, -4, -5, and -9 in cervical cancer [61,[63][64][65], TLR-9 in lung cancer [43], TLR-4, -5, -9 in gastric cancer [66], and TLR-2, -3, and -4 in colorectal cancer cells lines [67]. In general, TLR-4 and TLR-9 was found to be most strongly expressed in human cancer cells [32].…”

Toll-like Receptor

“…Embryonic fibroblasts, 38 cell lines 155 and cancer cells were also known to display various types of TLR. 156 It is important to study how different vital circumstances affect expression of TLRs in cell types and tissues, as well as examination of the difference between in vivo and in vitro.…”

Toll-Like Receptors as Novel Therapeutic Targets for the Treatment of Pancreatic Cancer

“…As previously described, chronic TLR activation and signaling in both immune and nonimmune cells by environmental antigens are now linked to oncogenesis, tumor growth, and invasive spread (Schmausser et al, 2005;Kelly et al, 2006;Fukata et al, 2007;He et al, 2007;Ilvesaro et al, 2007;Goto et al, 2008;Kim et al, 2008;Yoneda et al, 2008;Curtin et al, 2009;Xie et al, 2009;Zhou et al, 2009). Activation of TLR signaling results in the activation of transcription factors NF-ĸB and AP-1, as well as Type I Interferon (IFN) signaling pathways with subsequent production of "oncogenic" cytokines, and the activation of MAPK and AKT signaling pathways (Figure 1 prostate and many others ).…”