Producción CyT
Congreso
Autoría
MARTIN, AYELEN
;
María Celia Fernandez
;
Sofía Miraglia
;
Martín Medín
;
Patricia Papendieck
;
Florencia Clement
;
Elena De Matteo
;
Ana Chiesa
;
Patricia Pennisi
Fecha
2023
Editorial y Lugar de Edición
Karger AG
Resumen
Información suministrada por el agente en
SIGEVA
In pediatrics, thyroid tumor stratification is difficult to assess.Epithelial-mesenchymal transition (EMT), plays a role in tumordevelopment. In human carcinomas Brachyury (Brachy) has beenidentified as a regulator of EMT associated to malignancy. TheInsulin Like Growth Factors (IGFs) are mitogens that play importantroles in both normal and neoplastic growth. To date, no informationabout Brachy and IGF1R expression in pediatric thyroidnodular disease is available.Aim: To evaluate Brachy and IGF...
In pediatrics, thyroid tumor stratification is difficult to assess.Epithelial-mesenchymal transition (EMT), plays a role in tumordevelopment. In human carcinomas Brachyury (Brachy) has beenidentified as a regulator of EMT associated to malignancy. TheInsulin Like Growth Factors (IGFs) are mitogens that play importantroles in both normal and neoplastic growth. To date, no informationabout Brachy and IGF1R expression in pediatric thyroidnodular disease is available.Aim: To evaluate Brachy and IGF1R expression in thyroid nodularsamples from pediatric patients and to study the effect ofBrachy and IGF1R overexpression in a thyroid papillary carcinomacell line (TPC) in vitro. Methods: Paraffin-embedded samples from pediatric patientswith Thyroid Papillary Carcinomas (TPCa), Follicular Adenomas(FA) or Benign Thyroid Nodular disease (BTN) were processed forBrachy and IGF1R immunostaining. TPC cells were used to obtainclones overexpressing Brachy (TPC.BR4 and TPC.BR6) andIGF1R (TPC.IGF1R5 and TPC.IGF1R7). Gene expression wasquantified by rqPCR. Phaloidin IF staining, Viability and apoptosisassays (3 days) and wounding assays (24h) were carried out.Protein extracts were obtained from whole lysates and processedby western blotting (WB).Results: 50 samples were analysed, 17 from BTN. Only TPCaand FA showed positive staining for Brachy (15/24TPCa;5/9FA)and IGF1R (11/24TPCa;4/9FA). In carcinomas, positivity forIGF1R was only detected when Brachy was present. In vitro,Brachy overexpression in TPC cells increased proliferation(**p <0,01 TPC.BR4, ***p <0,005 TPC.BR6) while IGF1R overexpressionresulted in a lower proliferation rate (****p <0,0001) comparedto parental cells. Cell migration was also higher when Brachywas overexpressed (*p< 0.05 TPC.BR4 and TPC.BR6 vs TPC),e-cadherin expression was diminished, and mesenchymal markers(vimentin-fibronectin) were increased. The opposite profile wasfound in IGF1R overexpressing clones. Initial risk stratificationshowed an association between Brachy and high risk, while IGF1Rpositive immunostaining was associated with low risk initialassessment.Conclusion: Pediatric TPCa showed positive labeling for bothBrachy and IGF1R. While Brachy expression was associated tohigh risk, IGF1R expression was associated to low risk initial stratification.In vitro, Brachy overexpression led to a mesenchymal likephenotype in TPC.BR4 and TPC.BR6 clones. Conversely, IGF1Rexpression seems to favor epithelial features on TPC.IGF1R5 andTPC.IGF1R7 clones. These results suggest potential opposite rolesfor Brachy and IGF1R in the biology of thyroid tumors.
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Palabras Clave
CANCERTHYROIDIGF1RBRACHYURY