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Importance of ADAMTS-1 protease in local and systemic invasion of fibrosarcoma.

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Author(s):
Heydi Noriega Guerra
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Ruy Gastaldoni Jaeger; Alison Colquhoun; Fernanda Ortis; André Zelanis Palitot Pereira; Maria Aparecida da Silva Pinhal
Advisor: Vanessa Morais Freitas
Abstract

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. (AU)

FAPESP's process: 12/24108-2 - Role of ADAMTS-1 in local and systemic invasion of fibrosarcoma cells
Grantee:Heydi Noriega Guerra
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)