In vitro migration and cellular invasion of human cells expressing variants of the Epstein-Barr virus LMP1 oncoprotein

• Grant number: 14/06728-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: July 01, 2014
• End date: December 31, 2014
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Deilson Elgui de Oliveira
• Grantee: Nathália Suiti Laszkiewicz
• Supervisor: Ethel Cesarman
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Weill Cornell Medical College, United States
• Associated to the scholarship: 12/22335-1 - In vitro migration and cellular invasion of human cells expressing LMP1 EBV oncoprotein variants, BP.MS

Abstract

The Epstein-Barr virus (EBV) latently infects more than 90% of human adults. Viral infection is associated to the development of infectious mononucleosis, as well as some cancers, including Burkitt lymphoma, undifferentiated nasopharyngeal carcinoma, a subset of Hodgkin lymphomas, and lymphoproliferative disorders in immunocompromised hosts. Epithelial cells and B lymphocytes are the major target of EBV infection. Although the oncogenic potential of the virus is usually studied in terms of its capacity to transform the infected cells, some studies suggest that the EBV infection may also contribute to cancer progression. Latent membrane protein 1 (LMP1), the major EBV oncoprotein, has transforming properties both in vivo and in vitro. Several LMP1 variants are described, discriminated mainly by variations in its C-terminal and the transmembrane domains of the protein. Noteworthy, the LMP1 C-terminal domain activate intracellular signaling pathways that regulated cell migration; moreover, LMP1 upregulate the expression of cell proteins with roles in extracellular matrix remodeling and angiogenesis. Currently it is unknown whether different LMP1 variants possess distinct properties regarding biological phenomena relevant for cancer progression, notably for solid tumors. Thus, the present study aims to evaluate the in vitro behavior of cells expressing different LMP1 variants that may account for their biological aggressiveness. Cells will be transfected with expression vectors encoding for EBV LMP1 and evaluated regarding cellular motility and invasion capabilities using wound scratch repair and Boyden chamber assays, respectively. The data generated will be evaluated in order to clarify whether any LMP1 form evaluated would be associated with a distinct migratory or invasive behavior of the transfected cells. (AU)