Research Papers:

Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma

Lovisa Farnebo, Arash Shahangian, Yunqin Lee, June Ho Shin, Ferenc A. Scheeren and John B. Sunwoo _

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Oncotarget. 2015; 6:9897-9907. https://doi.org/10.18632/oncotarget.3393

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Lovisa Farnebo1,3, Arash Shahangian1,3, Yunqin Lee1,3, June Ho Shin1,3, Ferenc A. Scheeren2,3, John B. Sunwoo1,3

1Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA

2The Netherlands Cancer Institute, Amsterdam, The Netherlands

3Stanford Cancer Institute and the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA

Correspondence to:

John B. Sunwoo, e-mail: [email protected]

Keywords: head and neck cancer, inflammation, tumorigenesis

Received: December 12, 2014     Accepted: February 16, 2015     Published: April 02, 2015


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.

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