CONICET | Buscador de Institutos y Recursos Humanos

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/damage-associated molecular patterns. TLRs deregulation and polymorphisms have been implicated in 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 expression was detected on normal thyrocytes. Although high TLR4 levels were observed in all 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 cells with the TLR4 agonist lipopolyssacharide (LPS) increased IL-6 and iNOS expression. Interestingly, TLR4 stimulation induced the activation of the transcription factor NF-κB. Additionally, reduction of TLR4 expression by specific shRNA in thyroid tumor cells inhibited the LPS-induced NF-κB activation. Conclusions. Our results indicate that TLR4 is highly expressed in all tested thyroid carcinomas. Moreover, TLR4 signaling is functional in thyroid cancer cell lines. Overall, our findings raise an intriguing question about the role of TLR4 in thyroid malignancy, further considering that NF-κB has been implicated in cancer process.