Contributed by Guest Blogger: M. Aradi ’14
It has been recently discovered that exosomes are used by virally infected cells and cancer cells to manipulate their environment. The Epstein-Barr Virus, or EBV, significantly affects cell growth and leads to types of malignant cancer. The major oncogenic protein of EBV has been found to be LMP1, as it is often expressed with EBV cancers. Viruses use the exosomal pathway to leave cells and evade immune responses. It has been observed that LMP1 contributes to cell growth through the exosomal pathway. Exosomes generally transfer mRNA, micro RNA (miRNA) and proteins to other cells to affect cell proliferation, cell to cell communication and tumor cell invasion. LMP1’s most important target is the cellular EFGR protein, which is a cell growth-signaling receptor. EFGR is secreted from cells in exosomes, and then is taken up by epithelial cells where it functions for cell-growth pathways. It has also been discovered that cells infected with EBV release exosomes that contain LMP1, which inhibits T-cell functions.
The question was: What are the effects of LMP1 on exosomal composition and biochemical properties that support EBV cell infection? The test included two groups of EBV cells; first group contained low levels of LMP1, and the second group had higher expression levels of LMP1. The two group exosomes were tested for uptake potential by other cells, and it was found that the second group exosomes had a higher level of uptake. This shows that LMP1 plays a role in controlling exosomal proteins involved in cell adhesion and interaction. The two groups were exposed to epithelial cells and were observed for how the host cell signaling pathways were affected. It was found that the LMP1 exosomes induced higher levels of cell growth signaling pathways in recipient cells, showing that LMP1 contains protein factors that induce cell growth necessary for tumor growth and metastasis.
Although the study revealed certain key mechanisms of LMP1 function with EBV, further questions involve which specific exosomal proteins are manipulated by LMP1? How do LMP1 and EFGR interact to successfully induce cell growth? Which structure or pathway could possibly be targeted to prevent the spread of EBV and its tumor-inducing factors in efforts to cure cancer?