The expression and function of Toll-like receptors 3 and 9 in human colon carcinoma.

Abstract

Toll-like receptors (TLRs) are pattern-recognition receptors that are important in immune signaling. TLR recognition of various viral components including double-stranded RNA (TLR3) and unmethylated CpG-DNA (TLR9) plays a crucial role in cell survival. However, TLR expression and function in colon carcinoma cells are not well clarified. We investigated the expression of TLR3 and TLR9 in colon carcinoma cells using immunohistochemical methods. The function of TLR3 and TLR9 signaling in carcinoma cell lines was studied by direct cell stimulation with, or by cell transfection of, polyinosinic-polycytidylic acid (Poly I:C), a synthetic form of dsRNA, and by cell stimulation with CpG-oligodeoxynucleotides (ODNs), respectively. Positive TLR3 and TLR9 immunohistochemical staining was observed in 91 and 86% of human hepatocellular carcinoma (HCC) tissues, respectively. Cell surface stimulation of TLR3 with Poly I:C did not affect cell viability but it did activate NF-κB activity. By contrast, stimulation of intracellular TLRs with transfected Poly I:C significantly induced apoptosis. Cell surface stimulation of TLR9 with CpG-ODNs promoted cell proliferation, and, furthermore, these CpG-ODN TLR9 agonists reduced the cytotoxicity of the anticancer drug adriamycin. Cell surface expression of TLR3 and TLR9 in colon carcinoma cells plays an important role in cell survival. In addition, the proapoptotic activity of intracellularly expressed TLR3 may provide the possibility of using TLR3 agonists as novel clinical cytotoxic agents against colon carcinoma cells.

• Authors: Keiichiro Nojiri, Kazushi Sugimoto, Katsuya Shiraki, Masahiko Tameda, Yuuji Inagaki, Satoko Kusagawa, Suguru Ogura, Junichiro Tanaka, Misao Yoneda, Norihiko Yamamoto, Hiroshi Okano, Yoshiyuki Takei, Masaaki Ito, Chika Kasai, Hidekazu Inoue, Koujiro Takase
• Journal: Oncology reports (Oncol Rep) Vol. 29 Issue 5 Pg. 1737-43 (May 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 23467704 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• CPG-oligonucleotide
• NF-kappa B
• Oligodeoxyribonucleotides
• TLR3 protein, human
• TLR9 protein, human
• Toll-Like Receptor 3
• Toll-Like Receptor 9
• Doxorubicin
• Poly I-C

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, genetics)
• Cell Line, Tumor
• Cell Membrane (drug effects, genetics, metabolism)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects, genetics)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Doxorubicin (pharmacology)
• Humans
• NF-kappa B (genetics, metabolism)
• Oligodeoxyribonucleotides (genetics, metabolism)
• Poly I-C (pharmacology)
• Toll-Like Receptor 3 (agonists, genetics, metabolism)
• Toll-Like Receptor 9 (genetics, metabolism)