ANALYSIS OF THE BIOLOGICAL ROLE OF ACTIVIN A ON ANGIOGENESIS IN ORAL SQUAMOUS CELL CARCINOMAS

• Grant number: 13/19856-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2014
• End date: April 30, 2017
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Ricardo Della Coletta
• Grantee: Carine Ervolino de Oliveira
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Over the last few decades, it has become evident that tumor growth and metastasis are dependent on angiogenesis, the formation of new blood vessels from preexisting endothelium. Some studies have showed that tumor vasculature is the result of an imbalance between pro- and antiangiogenic factors secreted by tumor cells or tumor microenvironment cells. However, the complex interactions between those molecules and how they affect vessels structure and functioning in different tumors are not clarified. In this context, some studies suggest a role of activin A in angiogenesis, but little is known about the cellular pathways influenced by this factor, especially in oral tumorigenesis. Thus, the aim of this study is to analyze the role of activin A in angiogenesis-related growth and progression of oral squamous cell carcinomas (OSCC). To understand this role of activin A, we have compiled three specific objectives: 1) to evaluate the vascular density and the expression of activin A in OSCCs, correlating the expression levels with clinicopathological variabilities, recurrence and survival, 2) to analyze the biological effects produced by increased levels of activin A on human microvascular endothelial cells, and 3) to study the biological effects produced by activin A in the development of OSCC in vivo. Several studies suggest that the blockage of angiogenic factors may represent an excellent therapeutic target for OSCC, but little is known about the factors and mechanisms that control and coordinate the tumor vascularization, limiting this therapeutic possibility.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE ANDRADE, A. L. D. L.; DE OLIVEIRA, C. E.; DOURADO, M. R.; MACEDO, C. C. S.; WINCK, F. V.; PAES LEME, A. F.; SALO, T.; COLETTA, R. D.; DE ALMEIDA FREITAS, R.; GALVAO, H. C.. Extracellular vesicles from oral squamous carcinoma cells display pro- and anti-angiogenic properties. ORAL DISEASES, v. 24, n. 5, p. 725-731, JUL 2018. (13/19856-2)

DE OLIVEIRA, CARINE ERVOLINO; DOURADO, MAURICIO ROCHA; SAWAZAKI-CALONE, IRIS; DE MEDEIROS, MARCELL COSTA; ROSSA JUNIOR, CARLOS; CERVIGNE, NILVA DE KARLA; LEON, JORGE ESQUICHE; LAMBERT, DANIEL; SALO, TUULA; GRANER, EDGARD; et al. Activin A triggers angiogenesis via regulation of VEGFA and its overexpression is associated with poor prognosis of oral squamous cell carcinoma. International Journal of Oncology, v. 57, n. 1, p. 364-376, JUL 2020. (13/01607-6, 13/19856-2)