Laura K Mäkinen1, Abdirisak Ahmed2, Jaana Hagström3,4,5, Sanna Lehtonen3, Antti A Mäkitie1, Tuula Salo2,6, Caj Haglund7,8, Timo Atula1. 1. Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. 2. Institute of Dentistry, Biomedicum 1, University of Helsinki, Helsinki, Finland. 3. Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland. 4. Department of Pathology, HUSLAB, Helsinki University Hospital, Helsinki, Finland. 5. Department of Oral Pathology, Institute of Dentistry, University of Helsinki, Helsinki, Finland. 6. Department of Diagnostics and Oral Medicine, Institute of Dentistry, Oulu University Hospital and, University of Oulu, Oulu, Finland. 7. Department of Surgery, Helsinki University Hospital, Helsinki, Finland. 8. Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland.
Abstract
BACKGROUND: Toll-like receptors (TLRs) are pattern-recognizing proteins involved in innate immunity and they seem to regulate both cancer progression and inhibition. In oral cancer, TLR activation has been linked to invasion. To define the role of TLR-2, TLR-4, and TLR-9 in oral tongue squamous cell carcinoma (OTSCC), we studied their expression in vivo in OTSCC tumor samples, as well as in vitro in cell invasion model. METHODS: We used immunohistochemistry to compare the expression of TLR-2, TLR-4, and TLR-9 in 21 primary Stage I-II OTSCCs, neck metastases, and recurrent tumors. In addition, we used myoma organotypic invasion assay to evaluate the effect of GIT27 (4,5-dihydro-3-phenyl-5-isoxasoleaceticacid) on the invasion of the HSC-3 OTSCC cell line. RESULTS: TLR-2, TLR-4, and TLR-9 were expressed in most tumors. Nuclear TLR-2 expression occurred more often in primary tumors than in neck metastases or recurrent tumors of the neck, whereas nuclear TLR-4 expression and cytoplasmic TLR-9 expression were higher in primary tumors than in local recurrent tumors. GIT27 did not affect the invasion of HSC-3 OTSCC cells, but a myoma organotypic invasion assay revealed that the expression of TLR-2 and TLR-4 was stronger in deeper-invading cells. CONCLUSIONS: TLR-2, TLR-4, and TLR-9 were expressed in primary tumors, neck metastases as well as in recurrent tumors of OTSCC. Thus, these receptors seem to play a role in both the development and progression of tongue carcinoma. These TLRs may also contribute to the invasive potential of OTSCC.
BACKGROUND: Toll-like receptors (TLRs) are pattern-recognizing proteins involved in innate immunity and they seem to regulate both cancer progression and inhibition. In oral cancer, TLR activation has been linked to invasion. To define the role of TLR-2, TLR-4, and TLR-9 in oral tongue squamous cell carcinoma (OTSCC), we studied their expression in vivo in OTSCC tumor samples, as well as in vitro in cell invasion model. METHODS: We used immunohistochemistry to compare the expression of TLR-2, TLR-4, and TLR-9 in 21 primary Stage I-II OTSCCs, neck metastases, and recurrent tumors. In addition, we used myoma organotypic invasion assay to evaluate the effect of GIT27 (4,5-dihydro-3-phenyl-5-isoxasoleaceticacid) on the invasion of the HSC-3 OTSCC cell line. RESULTS:TLR-2, TLR-4, and TLR-9 were expressed in most tumors. Nuclear TLR-2 expression occurred more often in primary tumors than in neck metastases or recurrent tumors of the neck, whereas nuclear TLR-4 expression and cytoplasmic TLR-9 expression were higher in primary tumors than in local recurrent tumors. GIT27 did not affect the invasion of HSC-3 OTSCC cells, but a myoma organotypic invasion assay revealed that the expression of TLR-2 and TLR-4 was stronger in deeper-invading cells. CONCLUSIONS:TLR-2, TLR-4, and TLR-9 were expressed in primary tumors, neck metastases as well as in recurrent tumors of OTSCC. Thus, these receptors seem to play a role in both the development and progression of tongue carcinoma. These TLRs may also contribute to the invasive potential of OTSCC.
Authors: Pachiyappan Kamarajan; Islam Ateia; Jae M Shin; J Christopher Fenno; Charles Le; Ling Zhan; Ana Chang; Richard Darveau; Yvonne L Kapila Journal: PLoS Pathog Date: 2020-10-01 Impact factor: 6.823
Authors: Fernanda Visioli; Julia Silveira Nunes; Maria Carmela Pedicillo; Rosalia Leonardi; Angela Santoro; Gian Franco Zannoni; Gabriella Aquino; Margherita Cerrone; Monica Cantile; Nunzia Simona Losito; Vito Rodolico; Giuseppina Campisi; Giuseppe Colella; Ilenia Sara De Stefano; Maria Antonietta Ramunno; Cristina Pizzulli; Marco Visconti; Lorenzo Lo Muzio; Giuseppe Pannone Journal: Biomolecules Date: 2022-02-28