title: Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma.
abstract: Infection-driven inflammation has been proposed to be involved in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Oral HNSCC is often colonized with microbes such as gram-positive bacteria and yeast, where ligands derived from their wall components have been shown to specifically bind to Toll-like receptor 2 (TLR2). Although TLR2 has been described to be expressed in oral HNSCC, its function has not been well characterized. Here, we show the expression of TLR2 in both HNSCC cell lines and primary patient-derived HNSCC xenograft tumors. Activation of TLR2 with a yeast-derived ligand of TLR2, zymosan, promoted organoid formation in an ex vivo model of tumor growth, while blockade with anti-TLR2 antibodies inhibited organoid formation. Zymosan also induced phosphorylation of ERK and the p65 subunit of NF-κB, which was inhibited in the presence of anti-TLR2 antibodies, indicating that this receptor is functional in HNSCC and that the signaling through these pathways is intact. TLR2 blockade also inhibited growth of human xenografted tumors in immunodeficient mice. In summary, our data show that TLR2 is a functional receptor expressed in human HNSCC that plays a direct pro-tumorigenic role, and that it can be therapeutically targeted with blocking antibodies to reduce tumor growth.
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cancer Institute and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Lovisa
authors.initials: L
authors.lastname: Farnebo
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cancer Institute and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Arash
authors.initials: A
authors.lastname: Shahangian
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cancer Institute and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Yunqin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cancer Institute and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
authors.forename: June Ho
authors.initials: JH
authors.lastname: Shin
authors.affiliation: The Netherlands Cancer Institute, Amsterdam, The Netherlands.|Stanford Cancer Institute and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: Scheeren
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cancer Institute and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Sunwoo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D015054:Zymosan
keywords: head and neck cancer; inflammation; tumorigenesis
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