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Thèse de Doctorat
DOI
https://doi.org/10.11606/T.42.2018.tde-13032018-100002
Document
Auteur
Nom complet
Heydi Noriega Guerra
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2017
Directeur
Jury
Jaeger, Ruy Gastaldoni (Président)
Colquhoun, Alison
Ortis, Fernanda
Pereira, André Zelanis Palitot
Pinhal, Maria Aparecida da Silva
Titre en portugais
Importância da protease ADAMTS-1 na invasão local e sistêmica de células do fibrossarcoma.
Mots-clés en portugais
ADAMTS1
Fator de crescimento do hepatócito
Fator de crescimento transformante beta
Fibrossarcoma
Matriz extracelular
Metaloproteinases da matriz
Resumé en portugais
A matriz extracelular serve como depósito para fatores biologicamente ativos, como fatores de crescimento e proteases, os quais influenciam no comportamento das células tumorais. A ADAMTS-1 (uma desintegrina e metaloproteinase com motivos trombospondina) é um membro da família de metaloproteases ADAMTSs. Neste trabalho, avaliamos o papel da ADAMTS-1 na regulação das atividades estimuladas pelo HGF ou TGF-β1, sobre as células de fibrossarcoma (HT1080). A superexpressão de ADAMTS-1 afetou a proliferação e a velocidade de migração das células HT1080 estimuladas por HGF, mas não por TGF-β1. Demonstramos que a superexpressão da ADAMTS-1 diminuiu a fosforilação do receptor c-Met e das vias downstream ERK1/2 e FAK. Adicionalmente, na presença do HGF, a superexpressão de ADAMTS-1 perturbou a formação de fibrossarcosferas in vitro e microtumores in vivo. Esses microtumores e células individuais apresentaram características morfológicas de lesões menos invasivas. Nossos dados sugerem que a ADAMTS-1 regula as atividades estimuladas pelo HGF no fibrossarcoma.
Titre en anglais
Importance of ADAMTS-1 protease in local and systemic invasion of fibrosarcoma.
Mots-clés en anglais
ADAMTS1
Extracellular matrix
Fibrosarcoma
Hepatocyte growth factor
Matrix metalloproteinases
Transforming growth factor beta
Resumé en anglais
The extracellular matrix serves as a reservoir for biologically active factors, such as growth factors and proteases that influence the tumor cell behavior. ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we addressed the role played by ADAMTS-1 regulating HGF and TGF-β1 activities in fibrosarcoma cell line (HT1080). ADAMTS-1 overexpression affected the proliferation and migration velocity of HT1080 cells, after stimulation with HGF. However, ADAMTS-1 overexpression failed to affect TGF-β1 activity. We showed that ADAMTS-1 overexpression decreased the phosphorylation of c-Met receptor and downstream signaling pathways ERK1/2 and FAK. Additionally, in presence of HGF, ADAMTS-1 overexpression disrupted the formation of fibrosarcospheres in vitro and microtumors in vivo. These microtumors and individual cells presented characteristics of low invasive tumor cells (rounded morphology). Our results suggest that ADAMTS-1 is involved in regulating HGF-related functions on fibrosarcoma cells.
 
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Date de Libération
2020-03-12
Date de Publication
2018-03-13
 
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