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Medicina - OVEREXPRESSION OF BRACHYURY (BRACHY) AND INSULIN-LIKE GROWTH FACTOR RECEPTOR (IGF1R) IN THYROID PAPILLARY CARCINOMA (TPC) CELLS: DIFFERENT PHENOTYPES AND ASSOCIATION WITH PEDIATRIC THYROID NODULAR PATHOLOGY

Congress

Authorship
MARTIN, AYELEN ; Fernández, María Celia ; Miraglia, Sofía ; Papendieck, Patricia ; Clement Florencia ; De Matteo, Elena ; Chiesa, Ana ; Pennisi Patricia
Date
2024
Publishing House and Editing Place
Fundación Revista Medicina
Summary Information provided by the agent in SIGEVA
In pediatrics, thyroid tumor stratification is difficult to assess. In humancarcinomas Brachy has been identified as a regulator of Epithelial-mesenchymal transition. IGF1R play important roles in neoplasticgrowth. No information about Brachy and IGF1R expressionin pediatric thyroid nodular disease is available. Aim: To evaluateBrachy & IGF1R expression in pediatric thyroid nodular samplesand to study Brachy & IGF1R overexpression effect in vitro & in vivo.Methods: Immunostaining fo... In pediatrics, thyroid tumor stratification is difficult to assess. In humancarcinomas Brachy has been identified as a regulator of Epithelial-mesenchymal transition. IGF1R play important roles in neoplasticgrowth. No information about Brachy and IGF1R expressionin pediatric thyroid nodular disease is available. Aim: To evaluateBrachy & IGF1R expression in pediatric thyroid nodular samplesand to study Brachy & IGF1R overexpression effect in vitro & in vivo.Methods: Immunostaining for Brachy & IGF1R was performed inpediatric Thyroid Papillary Carcinomas (TPCa), Follicular Adenomas(FA) or Benign Thyroid Nodular disease (BTN). TPC cells overexpressingBrachy or IGF1R were used for Phaloidin staining, viability& apoptosis assays, wounding assays, gene (qPCR) & protein (WB)expression. Cells were injected in female nude mice (1e8cells/flank)Results: 50 samples were analyzed,17 from BTN. Only TPCa andFA showed positive staining for Brachy (15/24TPCa;5/9FA) and IGF1R(11/24TPCa;4/9FA). In TPCa, positivity for IGF1R was only detectedwhen Brachy was present. All patients with Brachy+/IGF1R immunostaining belonged to Intermediate/High-risk group and allbut one, persisted with Indeterminate/Incomplete response 2 yearspost-surgery. In vitro, Brachy overexpression increased proliferation(p<0.05vsTPC) and cell migration (p<0.05vsTPC), decreasede-cadherin and increased vimentin & fibronectin expression. The oppositeprofile was found in IGF1R overexpressing clones. In vivo, byd35 100% of tumors from Brachy cells had volumes above 60mm3,while those form TPC or IGF1R clones were smaller (p<0.001ANOVA).Conclusion: In TPCa Brachy+/IGF1R- staining was associatedwith initial higher risk and indeterminate/incomplete response at2 years. In vitro Brachy overexpression led to a mesenchymal likephenotype and favored tumor growth. Conversely, IGF1R expressionfavored epithelial features. Results suggest potential oppositeroles for Brachy and IGF1R Thyroid tumor biology.
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Key Words
IGF1RBRACHYURY