Agrin has a pathological role in the progression of oral cancer

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: BRITISH JOURNAL OF CANCER; v. 118, n. 12, p. 1628-1638, JUN 2018.
• Web of Science Citations: 2

Abstract

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)

• FAPESP's process: 09/54067-3 - Acquisition of a mass spectrometer coupled to a liquid chromatography system for increasing the capacity to meet the needs of users and for making new technologies available in the Laboratory of Mass Spectrometry
• Grantee: Adriana Franco Paes Leme
• Support type: Multi-user Equipment Program
• FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
• Grantee: Adriana Franco Paes Leme
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 16/07846-0 - Peptidomic analysis of extracelular vesicles originated from cell lines, saliva and plasma from oral squamous cell carcinoma
• Grantee: Adriana Franco Paes Leme
• Support type: Regular Research Grants