Agrin has a pathological role in the progression of oral cancer

Autor(es)

Rivera, Cesar ^{[1, 2, 3]} ; Zandonadi, Flavia Silva ^[1] ; Sanchez-Romero, Celeste ^[2] ; Soares, Ciro Dantas ^[2] ; Granato, Daniela Campos ^[1] ; Alejandro Gonzalez-Arriagada, Wilfredo ^[4] ; Paes Leme, Adriana Franco ^[1]

Afiliação do(s) autor(es)

^[1] CNPEM, LNBio, Lab Nacl Biociencias, Lab Espectrometria Massas, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Fac Odontol Piracicaba, Piracicaba - Brazil

^[3] Univ Talca, Fac Ciencias Salud, Dept Ciencias Basicas Biomed, Talca - Chile

^[4] Univ Valparaiso, Fac Odontol, Valparaiso - Chile

• Tipo de documento: Artigo Científico
• Fonte: BRITISH JOURNAL OF CANCER; v. 118, n. 12, p. 1628-1638, JUN 2018.
• Citações Web of Science: 2

Resumo

BACKGROUND: The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin-a member of this matrix-in progression of oral squamous cell carcinoma (OSCC). METHODS: We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics. Finally, we evaluated the clinical relevance of agrin interactome. RESULTS: Agrin was elevated in malignant and premalignant lesions. Further, we show that agrin silencing interferes with cancer cell motility, proliferation, invasion, colony and tumour spheroid formation, and it also reduces the phosphorylation of FAK, ERK and cyclin D1 proteins in OSCC cells. In orthotopic model, agrin silencing reduces tumour aggressiveness, like vascular and neural invasion. From a clinical perspective, agrin contextual hubs predict a poor clinical prognosis related with overall survival. CONCLUSIONS: Altogether, our results demonstrate that agrin is a histological marker for the progression of oral cancer and is a strong therapeutic target candidate for both premalignant and OSCC lesions. (AU)

• Processo FAPESP: 16/07846-0 - Análise peptidômica de vesículas extracelulares originadas de linhagens celulares, saliva e plasma de pacientes com carcinoma de células escamosas da cavidade oral
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS)
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários