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Doctoral Thesis
DOI
10.11606/T.5.2006.tde-26052006-113740
Document
Author
Full name
Andreia Hanada Otake
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2005
Supervisor
Committee
Chammas, Roger (President)
Barbuto, Jose Alexandre Marzagao
Benard, Gil
Neves, Rogerio Izar
Pueyo, Shigueko Sonohara Troyano
Title in Portuguese
"Papel de dissialogangliosídios na proliferação e morte celular induzida de melanócitos e melanomas in vitro"
Keywords in Portuguese
Divisão celular
Fatores de crescimento de fibroblastos
Gangliosídeos
Melanoma
Morte celular
Quimioterapia
Abstract in Portuguese
Dissialogangliosídios, como GD3 e derivados são marcadores da progressão de melanomas. Para avaliar as possíveis funções desta molécula, transfectamos células de melanócitos com o gene da enzima ST8Sia I, que converte GM3 em GD3. Mostramos que GD3 não interfere na capacidade proliferativa dessas células, porém a expressão de GD3 mostrou-se associada à sobrevivência celular. Melanomas adquirem autonomia quanto às vias dependentes do fator de crescimento de fibroblastos (FGF-1 e -2). A expressão de GD3 não interfere na resposta proliferativa a estes fatores, porém GD3 e outros glicoesfingolipídios de membrana modulam a resposta migratória induzida por FGF-2. A expressão de GD3 sensibiliza as células à morte celular induzida por diferentes quimioterápicos, como cisplatina e vimblastina; porém, torna as células resistentes ao tratamento com temozolamida. A sensibilização ao tratamento com vimblastina, mas não às outras drogas, depende da presença de GD3, como observado por ensaios de depleção metabólica
Title in English
Role of disialogangliosides in proliferation and induced cell death of melanocytes and melanomas in vitro
Keywords in English
Cell death
Cell division
Drug therapy
Fibroblast growth factors
Gangliosides
Melanoma
Abstract in English
Disialoganglioside GD3 and its derivatives are melanoma progression markers. To evaluate the possible roles of these molecules along melanoma progression, we have transfected the GD3 synthase gene (ST8Sia I) in a melanocyte cell line. Accumulation of GD3 did not confer any proliferative advantage to melanocytes. However, GD3 expression was associated with cell survival. The autonomic growth of melanomas is in part related to a constitutive activation of fibroblast growth factor dependent pathways. GD3 expression did not alter the proliferative response to either FGF-1 or FGF-2. However, GD3 and other membrane glycospingolipids modulate the motogenic activity of FGF-2. GD3 expression sensitizes melanocytes to chemotherapeutic agent-induced cell death, as cisplatin and vimblastin. On the other hand, GD3 turned melanocytes more resistant to temozolomide. Chemosensitization to vimblastin, but not to the other drugs, was dependent on the presence of GD3 within the cells, as shown by metabolic depletion of glycosphingolipids
 
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andreiahotake.pdf (5.56 Mbytes)
Publishing Date
2006-06-02
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
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  • OTAKE, Andreia Hanada, DUARTE, A. P. M., and CHAMMAS, R. FGF-2 motogenic, but not mitogenic, activity depends on glycosphingolipid composition of melanocyte cell membranes. In SIMEC2002-Simposio Internacional sobre Matriz Extracelular, Angra dos Reis, 2002. SIMEC2002-Program and Abstract Book., 2002. Abstract.
  • OTAKE, Andreia Hanada, DUARTE, A. P. M., and CHAMMAS, R. The motogenic activity of FGF depends on glycosphingolipid composition of melanocyte cell membranes. In XXXII Reunião Anual da Sociedade Brasileira de Bioquímica e Biologia Molecular, Caxambu, 2003. Livro de Resumos- XXXII Reunião Anual da SBBq., 2003. Abstract.
  • OTAKE, Andréia Hanada, DUARTE, A. P. M., e CHAMMAS, R. Gangliosides modulate melanocyte migration. In I Simpósio Avanços em Pesquisas Médicas dos Laboratórios de Investigação Médica do HC-FMUSP, São Paulo, 2003. Resumo. Dispon?vel em: http://www.usp.br/medicina/direxlim.
  • TORTELLI JR, Tharcisio Citrangulo, et al. Subcellular localization of prohibitin in cisplatin-treated human melanoma cells. In XXXVI Reunião Anual da SBBq, Salvador, 2007. Anais da XXXVI Reunião Anual da SBBq., 2007. Abstract.
  • CHAMMAS, R., et al. Genética e Biologia Molecular do Melanoma e de sua Progressão. In Renato Santos de Oliveira Filho. Melanoma Cutâneo Localizado e Linfonodo Sentinela. Organizador. São Paulo : LeMar, 2003{Volume}, p. 1-19.http://www.teses.usp.br/teses/disponiveis/5/5155/tde-26052006-113740/
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