Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 65
Increased expression of high mobility group box 1 (HMGB1) protein is associated with
an elevated level of iNOS in lymphocytic thyroiditis and papillary thyroid cancer.
Stefania Mardente, Gianluca Maiani, Emanuela Mari, Alessandra Zicari, Massimo
Realacci, Stefania Natalizi, Fabrizio Consorti*, Carlo Della Rocca and Alfredo
Antonaci*.
Department of Experimental Medicine and Pathology and * Department of Surgical
Sciences and Applied Technologies, University “La Sapienza”, Viale Regina Elena 324,
Rome Italy: email: stefania.mardente@uniroma1.it
Some recent works have shown that autoimmune thyroiditis, although considered a benign
condition often harbours a genetic rearrangement that is highly specific for papillary
carcinoma. Submicroscopic foci of papillary carcinoma exist in autoimmune thyroiditis
although its behaviour is still benign. We have recently demonstrated that peripheral
lymphocytes (type Tc1 and Tc2) infiltrate thyroids in autoimmune thyroiditis and in most
papillary carcinomas. Direct cytotoxicity, secretion of cytokines, presence of intrathyroidal B
secreting autoantibodies, would altoghether work as a defect in suppressing the immune
process. The local inflammation would lead to secretion of NO that could exacerbate the
autoimmune response and hypothyroidism. It has been demonstrated that high concentrations
of NO are genotoxic in the sense of promoting mutations that could lead to cancer. Local
hypoxia and high concentrations of NO may induce apoptosis of thyreocytes in chronic
inflammation and cancer but it may also lead to necrotic death. HMGB1 is a non histone
chromosomal protein implicated in a variety of processes including transcription,
differentiation and development. An increased expression of this protein has been reported for
several tumor types. Its overexpression inhibits apoptosis. According to our western blot
analysis of primary cultures of thyreocytes from patients with thyroiditis and papillary cancer
and immunohistochemistry of iNOS, we identified a molecular pathway triggered by HMGB1
that could inhibit apoptosis of thyreocytes in a microenvironment rich of NO and other
proinflammatory cytokines.
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