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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-13032018-100002
Document
Author
Full name
Heydi Noriega Guerra
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Jaeger, Ruy Gastaldoni (President)
Colquhoun, Alison
Ortis, Fernanda
Pereira, André Zelanis Palitot
Pinhal, Maria Aparecida da Silva
Title in Portuguese
Importância da protease ADAMTS-1 na invasão local e sistêmica de células do fibrossarcoma.
Keywords in Portuguese
ADAMTS1
Fator de crescimento do hepatócito
Fator de crescimento transformante beta
Fibrossarcoma
Matriz extracelular
Metaloproteinases da matriz
Abstract in Portuguese
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.
Title in English
Importance of ADAMTS-1 protease in local and systemic invasion of fibrosarcoma.
Keywords in English
ADAMTS1
Extracellular matrix
Fibrosarcoma
Hepatocyte growth factor
Matrix metalloproteinases
Transforming growth factor beta
Abstract in English
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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Release Date
2020-03-12
Publishing Date
2018-03-13
 
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