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Doctoral Thesis
DOI
10.11606/T.87.2018.tde-08022018-141249
Document
Author
Full name
Rodrigo Pinheiro Araldi
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Stocco, Rita de Cassia (President)
Carvalho, Rodrigo Franco de
Cerutti, Janete Maria
Gaspari, Elizabeth Natal de
Sá Junior, Paulo Luiz de
Souza, Edislane Barreiros de
Title in Portuguese
Linhagens celulares derivadas de cultivos primários de neoplasias infectadas pelo BPV como modelo de estudo da transição epitélio-mesênquima.
Keywords in Portuguese
BPV
Cultivo celular
Oncologia
Transição epitélio-mesênquima
Abstract in Portuguese
A ação metastática do BPV permanece não clara. Este estudo avaliou a ação do BPV na transição epitélio-mesênquima (TEM), empregando linhagens celulares de papiloma (P), fibropapiloma (FB) e carcinoma de esôfago (CE). Os resultados mostraram a presença de infecção produtiva e o aumento do potencial proliferativo nestas células. Porém, foi verificada a redução do potencial de membrana mitocondrial em relação à pele saudável (controle) e o aumento do estresse oxidativo, resultante da ação da oncoproteína E6, justificando a clastogenicidade e a aquisição do fenótipo-tronco descrito nas linhagens de P, FB e CE. Estas linhagens mostram capacidade migratória decorrente do sequestro citoplasmático de E-caderina, e o aumento dos níveis de expressão de vimentina, vinculina e N-caderina como consequência da ativação dos fatores STAT3 e SLUG, sugerindo a ação do vírus na indução da TEM. Tais resultados foram validados em amostras de tecido, reforçando a ação do vírus na TEM, bem como demostrando o potencial destas linhagens celulares como modelo de estudo da metástase.
Title in English
Cell lines derived from BPV-infected neoplasms primary cultures as model to study epitelial-mesenchymal transition.
Keywords in English
BPV
Cell culture
Epithelial-mesenchymal transition
Oncology
Abstract in English
BPV metastatic action remains unclear. This study evaluated the BPV action on epithelial-mesenchymal transmition (EMT), using cell lines form papilloma (P), fibropapilloma (FB) and esophageal carcinoma (EC). Results showed the productive infection presence and the proliferative potential increase in these cells. However, it was verified the mitochondrial membrane potential loss in relation to normal skin (control) and the oxidative stress increase as result of E6 oncoprotein, justifying the clastogenicity and stem-cell phenotype acquisition described in P, FB and EC cells. This cell lines showed a migratory capability as result of cytoplasmic sequester of E-cadherin, and the increase levels of vimentin, vinculin and N-cadherin as consequence of STAT3 and SLUG factors activation, suggest the virus action on EMT. These results were also verified in tissue samples, reinforcing the BPV action on EMT, as well as demonstrating the potential of these cell lines as model to study the metastasis.
 
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Publishing Date
2018-10-01
 
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