In vitro migration and cellular invasion of human cells expressing LMP1 EBV oncoprotein variants

Abstract

The Epstein-Barr virus latently infects more than 90% of the human population. The viral infection is associated with the development of infectious mononucleosis and some cancers, including Burkitt lymphoma, undifferentiated nasopharyngeal carcinoma, some cases of Hodgkin lymphoma and lymphoproliferative post-transplant disorders. Epithelial cells and B lymphocites are the main targets to EBV infection. Although usually the oncogenic virus is attributed to its capacity to transform infected cells, some studies suggest that viral infection may also contribute to the EBV progression cancer. The latent membrane protein 1 (Latent membrane protein 1 - LMP1) is the main product of EBV with transforming properties, both in vitro and in vivo. LMP1 different variants are described mainly by changes in the transmembrane domain and carboxy - terminal of the protein. Of note, the C -terminal domain of LMP1 is able to activate intracellular signaling pathways that regulate the phenomena of cell migration and invasion; additionally LMP1 induce synthesis of products that degrade the extracellular matrix and promotes angiogenesis. So far it is not known whether different LMP1 variants have different properties with respect to these important phenomena of tumor progression, particularly for solid tumors. Therefore, this study aims to evaluate in vitro parameters related to the dissemination of cancers in cells expressing LMP1 different variants. For this purpose, HEK293 cells will be transfected with expression vectors containing LMP1 and subjected to experiments to evaluate the migratory capacity and in vitro invasion in order to identify any differences that can be attributed to variations found in different forms of LMP1 analyzed. (AU)