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Master's Dissertation
DOI
10.11606/D.42.2011.tde-26012012-103529
Document
Author
Full name
Camila Fernandes Nascimento
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Jaeger, Ruy Gastaldoni (President)
Carvalho, Hernandes Faustino de
Santos, Marinilce Fagundes dos
Title in Portuguese
Papel de peptídeos bioativos da laminina na atividade dos invadopódios em linhagem celular derivada de carcinoma adenóide cístico.
Keywords in Portuguese
Adenóides
Carcinoma
Células cultivadas de tumor
Neoplasias da glândulas salivares
Peptídeos
Abstract in Portuguese
Carcinoma adenóide cístico é uma neoplasia maligna de glândula salivar com alto grau de recorrência e metástase. Células tumorais que invadem tecidos subjacentes formam invadopódios, protrusões de membrana ricas em actina, cortactina e MT1-MMP capazes de degradar a matriz extracelular (MEC). Proteólise de moléculas da MEC, como a laminina, promove liberação de fragmentos e peptídeos bioativos. Nesse trabalho, estudamos o papel dos peptídeos AG73 e C16, da laminina-111, na atividade de invadopódios de células derivadas de carcinoma adenóide cístico (CAC2). Nossos resultados mostram que AG73 e C16 regulam atividade de invadopódio e aumentam a expressão de MT1-MMP em células CAC2. Silenciamento da integrina b1 e inibição da via ERK diminuem a atividade de invadopódio induzida por esses peptídeos. Já a inibição da via Rac diminui a atividade de invadopódios induzida apenas por AG73. Propomos que os peptídeos AG73 e C16 regulariam a atividade de invadopódios através da integrina b1 e da via ERK 1/2. Já a via Rac1 transduziria sinais gerados apenas pelo peptídeo AG73.
Title in English
Role of laminin-111 derived peptides in invadopodia activity of a human adenoid cystic carcinoma cell line.
Keywords in English
Adenoids
Carcinoma
Neoplasms of the salivary glands
Peptides
Tumor cells grown
Abstract in English
Adenoid cystic carcinoma is a frequently occurring malignant salivary gland neoplasm with high level of recurrence and metastasis. Tumor cells that invade surrounding tissues rely on invadopodia to degrade extracellular matrix (ECM). Invadopodia are actin and cortactin-rich membrane protrusions that localize MT1-MMP required for ECM degradation. Breakdown of ECM molecules, such as laminins, releases fragments and bioactive peptides. Here we addressed the role of laminin-111 peptides AG73 and C16 in invadopodia activity of cells derived from human adenoid cystic carcinoma (CAC2). Our results show that AG73 and C16 increase invadopodia activity and MT1-MMP expression in CAC2 cells. Silencing of b1 integrin and ERK pathway inhibition decrease AG73 and C16-induced invadopodia. Rac1 pathway inhibition decreases only AG73-induced invadopodia formation. We propose that AG73 and C16 increase invadopodia activity in CAC2 cells through b1 integrin. ERK1/2 pathway would transduce signals generated by both peptides, while Rac1 pathway is related to AG73 signaling.
 
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Publishing Date
2012-02-13
 
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