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Toll‐like receptors 2, 4, and 9 in primary, metastasized, and recurrent oral tongue squamous cell carcinomas
Author(s) -
Mäkinen Laura K.,
Ahmed Abdirisak,
Hagström Jaana,
Lehtonen Sanna,
Mäkitie Antti A.,
Salo Tuula,
Haglund Caj,
Atula Timo
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12373
Subject(s) - innate immune system , cancer research , biology , toll like receptor , receptor , pathology , cell , immunohistochemistry , cancer , immune system , medicine , immunology , biochemistry , genetics
Background Toll‐like receptors ( TLR s) 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 OTSCC s, neck metastases, and recurrent tumors. In addition, we used myoma organotypic invasion assay to evaluate the effect of GIT 27 (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. GIT 27 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 TLR s may also contribute to the invasive potential of OTSCC .