title: Activation of Toll-like receptor 3 induces apoptosis of oral squamous carcinoma cells in vitro and in vivo.
abstract: Toll-like receptors are well known as molecular sensors of pathogen-associated molecular patterns. They control activation of the innate immune response and subsequently shape the adaptive immune response. Recent publications have demonstrated that Toll-like receptors also play important roles in multiple human cancers, yet their function in oral squamous cell carcinoma remains unclear. In this study, we showed that both oral squamous cell carcinoma cell lines and tissues from oral squamous carcinoma patients express relatively high levels of Toll-like receptor 3. We also found that synthetic dsRNA-polyinosinic-polycytidilic acid, a Toll-like receptor 3 ligand, induced apoptosis of oral squamous carcinoma cells mainly via Toll-like receptor 3, through interferon-β production and activation of caspases 3 and 9. Moreover, in an oral squamous cell carcinoma xenograft mouse model, we demonstrated for the first time that activation of Toll-like receptor 3 inhibited oral squamous cell carcinoma tumor growth in vivo. Therefore, the direct proapoptotic activity of Toll-like receptor 3 in human oral squamous carcinoma cells may make this protein a viable therapeutic target in the treatment of oral squamous cell carcinoma.
authors.affiliation: Department of Clinical Laboratories, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Qingqiong
authors.initials: Q
authors.lastname: Luo
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Zujun
authors.initials: Z
authors.lastname: Sun
authors.forename: Wantao
authors.initials: W
authors.lastname: Chen
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D053148:Caspase 3; D053453:Caspase 9; D011070:Poly I-C