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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2008.tde-30052008-123952
Document
Author
Full name
Karina Lawrence Ramos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Colquhoun, Alison (President)
Bittencourt, Jackson Cioni
Carvalho, Hernandes Faustino de
Chammas, Roger
Santelli, Glaucia Maria Machado
Title in Portuguese
Análise comparativa das distribuições espaciais de moléculas envolvidas na migração e invasão de um tumor cerebral de rato in vivo.
Keywords in Portuguese
Angiogênese
Células cultivadas de tumor
Matriz extracelular
Moléculas de adesão celular
Ratos
Sistema nervoso central
Abstract in Portuguese
O Glioblastoma multiforme (GBM) é o mais maligno tumor cerebral e apresenta uma alta capacidade proliferativa, invasiva e angiogênica. Neste estudo foi avaliada a distribuição espacial de moléculas envolvidas nesses processos num modelo de GBM de rato in vivo (C6). Por imunohistoquímicas observou-se que o tumor foi capaz de expressar diferentes elementos de matriz extracelular (colágenos I, III e IV, fibronectina, tenascinas C e R, vitronectina e proteoglicanos), moléculas de adesão (RHAMM, CD44 e integrinas) e a enzima proteolítica MMP-2. Esses elementos parecem se organizar num padrão pericelular nas células invasivas das bordas do tumor e nas células C6 migrando pelos vasos. A expressão de moléculas de adesão mostrou que o RHAMM pode ter um papel mais importante que o CD44 no reconhecimento do ácido hialurônico. A expressão de flt-1 e flk-1 pelas células tumorais sugere um papel desses receptores do VEGF não apenas na proliferação endotelial, mas também na proliferação tumoral. Todas as moléculas aqui analisadas são potenciais alvos terapêuticos futuros.
Title in English
Comparative analysis of spatial distribution of molecules related to migration an invasion in a rat brain tumor in vivo.
Keywords in English
Adhesion molecules
Angiogenesis
Central nervous system
Extracellular matrix
Rat
Tumor cultivated cells
Abstract in English
Glioblastoma multiforme (GBM) is the most malignant brain tumour and presents high proliferative, invasive and angiogenic capacities. In the present study the spatial distribution of molecules involved with these processes was analyzed in a rat GBM (C6) in vivo. Immunohistochemical analysis showed that tumours expressed extracellular matrix elements (collagens I, III and IV, fibronectin, tenascin C and R, vitronectin and proteoglycans), adhesion molecules (RHAMM, CD44 and integrins) and the proteolytic enzyme MMP-2. At the tumour borders and around the cells migrating along blood vessels these molecules seemed to organize in a pericellular pattern. The adhesion molecules analysis showed that RHAMM could have a pivotal role in hyaluronic acid recognition. Flt-1 and flk-1 expression by tumour cells suggests a role for these VEGF receptors not only in endotheliocyte metabolism, but also in tumour proliferation. All of the studied molecules are potential targets for anti-cancer therapies.
 
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Publishing Date
2008-06-10
 
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