Producción CyT
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

Congreso

Autoría
MARTIN, AYELEN ; Fernández, María Celia ; Miraglia, Sofía ; Papendieck, Patricia ; Clement Florencia ; De Matteo, Elena ; Chiesa, Ana ; Pennisi Patricia
Fecha
2024
Editorial y Lugar de Edición
Fundación Revista Medicina
Resumen Información suministrada por el agente en 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.
Ver más Ver menos
Palabras Clave
IGF1RBRACHYURY