Background. Toll like receptors (TLRs) comprise a family of membrane proteins related to the Interleukin (IL)-1 receptor. TLRs mediate host defense against infection and injury by recognizing pathogen- and damage-associated molecular patterns. TLRs deregulation and polymorphisms have been implicated in a number of noninfectious diseases, including autoimmunity and cancer. Interestingly, we have recently shown that TLR4 is functionally expressed in thyrocytes; although its role in thyroid pathologies remains obscure.
Objective. To evaluate TLR4 expression and function in thyroid tumors.
Methods. TLR4 expression was evaluated in normal (n=15) and malignant thyroid sections, including papillary (n=18), follicular (n=20), and anaplastic (n=4) thyroid carcinomas by immunohistochemistry. Functional TLR4 expression was analyzed in the thyroid cancer cell lines WRO and TPC-1.
Results. TLR4 protein was expressed on normal thyrocytes. Although high TLR4 protein levels were observed in 100% of the analyzed thyroid malignancies, such overexpression was absent in adjacent normal tissue.
Coincidently, basal TLR4 expression was detected in thyroid cancer cell lines. Moreover, treatment of malignant thyroid cells with the TLR4 agonist lipopolyssacharide (LPS) increased IL-6 and iNOS mRNA expression. Interestingly, TLR4 stimulation induced the activation of the transcription factor NF-êB.
Additionally, reduction of TLR4 expression by specific shRNA in thyroid tumor cells inhibited the LPS-induced NF-êB activation.
Conclusions. The presented data indicate that TLR4 is highly expressed in all tested thyroid carcinomas in vivo. Analysis in vitro showed that TLR4 signal system is functional in WRO and TPC-1 cell lines. Overall, our findings raise an intriguing question about the role of TLR4 in thyroid malignancy, further considering that NFkB has been implicated in cancer process.
