Mäkinen Laura K, Ahmed Abdirisak, Hagström Jaana, Lehtonen Sanna, Mäkitie Antti A, Salo Tuula, Haglund Caj, Atula Timo
Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Institute of Dentistry, Biomedicum 1, University of Helsinki, Helsinki, Finland.
J Oral Pathol Med. 2016 May;45(5):338-45. doi: 10.1111/jop.12373. Epub 2015 Oct 1.
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.
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.
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.
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.
Toll样受体（TLRs）是参与先天免疫的模式识别蛋白，它们似乎既能调节癌症进展，也能抑制癌症。在口腔癌中，TLR激活与侵袭有关。为了明确TLR-2、TLR-4和TLR-9在口腔舌鳞状细胞癌（OTSCC）中的作用，我们研究了它们在OTSCC肿瘤样本中的体内表达情况，以及在细胞侵袭模型中的体外表达情况。
我们采用免疫组织化学方法比较了21例I-II期原发性OTSCC、颈部转移瘤和复发性肿瘤中TLR-2、TLR-4和TLR-9的表达。此外，我们使用肌瘤组织型侵袭试验评估GIT27（4,5-二氢-3-苯基-5-异恶唑乙酸）对HSC-3 OTSCC细胞系侵袭的影响。
大多数肿瘤中都表达TLR-2、TLR-4和TLR-9。核TLR-2表达在原发性肿瘤中比在颈部转移瘤或颈部复发性肿瘤中更常见，而核TLR-4表达和细胞质TLR-9表达在原发性肿瘤中高于局部复发性肿瘤。GIT27不影响HSC-3 OTSCC细胞的侵袭，但肌瘤组织型侵袭试验显示，TLR-2和TLR-4在侵袭更深的细胞中表达更强。
TLR-2、TLR-4和TLR-9在原发性OTSCC肿瘤、颈部转移瘤以及复发性肿瘤中均有表达。因此，这些受体似乎在舌癌的发生和发展中都发挥作用。这些TLRs也可能有助于OTSCC的侵袭潜能。
