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Master's Dissertation
DOI
10.11606/D.42.2014.tde-20022015-100537
Document
Author
Full name
Lívia Caires dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Jaeger, Ruy Gastaldoni (President)
Cardoso, Alexandre Bruni
Gama, Patricia
Title in Portuguese
Peptídeo C16 regula migração, invasão, invadopódios e suas moléculas-chave, bem como geração de espécies reativas de oxigênio em células tumorais prostáticas.
Keywords in Portuguese
Câncer prostático
Espécies reativas de oxigênio
Invadopódios
Laminina
Matriz extracelular
Tks
Abstract in Portuguese
O câncer de próstata é o segundo câncer mais freqüentemente diagnosticado em homens. Durante o crescimento tumoral, as células neoplásicas interagem com a matriz extracelular (MEC). Analisamos o efeito de C16, peptídeo derivado da clivagem da MEC, sobre a migração, invasão e regulação dos invadopódios em células de câncer de próstata (DU145). Ensaios de migração e invasão demonstraram que C16 promoveu um aumento da atividade migratória e invasiva de células DU145 de maneira dose dependente. Demonstramos que o peptídeo estimula a fosforilação de Src. Ensaios de degradação em substrato fluorescente mostraram que C16 promoveu a formação de invadopódios de células DU145. O immunoblot nos revelou que este peptídeo também estimula a expressão de Tks4, Tks5, cortactina e MT1-MMP. C16 estimulou a produção de espécies reativas de oxigênio, importantes para o fenótipo invasivo das células tumorais. Nossos resultados sugerem que o peptídeo C16 regula migração, invasão, invadopódios e suas moléculas-chave e a geração de espécies reativas de oxigênio em células DU145.
Title in English
Laminin-derived peptide C16 regulates migration, invasion, invadopodia key-molecules, and ROS generation in human prostate cancer cells.
Keywords in English
Extracellular matrix
Invadopodia
Laminin
Prostate cancer
ROS
Tks
Abstract in English
Prostate cancer is the second most frequently diagnosed cancer in males. During tumor growth, neoplastic cells interact with the extracellular matrix (ECM) Our Laboratory has demonstrated that peptides derived from ECM cleavage are involved in migration, invasion and invadopodia formation in different tumor cell lines. Invadopodia activity depends on expression of the proteins Tks4, Tks5, cortactin, MT1-MMP, as well as reactive oxygen species (ROS) generation. Migration and invasion assays in chemotaxis chambers demonstrated that C16 increased migration and invasion activities of DU145 cells in a dose-dependent manner. We observed that the peptide stimulated phosphorylation of Src. Fluorescent substrate degradation assay showed that C16 increased invadopodia activity of DU145 cells. Immunoblot revealed that this peptide stimulated Tks4, Tks5, cortactin and MT1-MMP expression. Furthermore, C16 increased ROS production. Our results strongly suggested that C16 regulates migration, invasion, invadopodia key-molecules, and ROS generation in DU145 cells.
 
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Release Date
2017-02-19
Publishing Date
2015-02-20
 
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