Tag Archives: Exosome

Exit Pathway for Cancer-inducing Virus

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?


Exosomes Signaling Surroundings

Contributed by Guest Blogger: E. Raganit ’14

Epstein-Barr virus (EBV), also known as Human Herpes virus 4, greatly influences the development of many cancers. Latent membrane protein 1 (LMP1) was found to be an important oncogene of EBV in that it has transforming properties. Exosomes, vesicles that are secreted to aid in the transfer of proteins, mRNAs, and microRNAs to neighbor cells, have just recently been discovered as a mechanism that may be manipulated by both cancer cells and virus-infected cells. They are found in many biological fluids, including blood and urine. It was also recently concluded that viruses may use the exosome pathway to evade the immune system.
In a study done by the Lineberger Comprehensive Cancer Center and the Department of Microbiology-Immunology of the University of North Carolina, the group of scientists wished to test the effects of LMP1 on the exosome composition. The group harvested cells from the nasopharyngeal cell (NPC) C666 cell line that retained EBV, but also had low levels of LMP1 and compared it to both a C666 line that strongly expressed LMP1 exosomes (C666-LMP1) and a C666 control (C666-pBabe). Both the C666 and the C666-LMP1 exsosomes contained epidermal growth factor receptors.
In a test to determine if LMP1 had the ability to activate signaling pathways, the scientists exposed human umbilical vein endothelial cells (HUVECs) to exosomes. Results showed that the C666-pBabe exosomes were capable of activating the signaling pathways, but the C666-LMP1 exosomes induced activation in higher levels. This led to the conclusion that LMP1 increased the release of the epidermal growth factor receptor into exosomes, causing the activation of the ERK pathways. Findings also showed that EBV virus used the exosomal system in order to secrete molecules and viral-encoded proteins.
With the knowledge that through these exosome pathways, viruses may escape the immune system with the LMP1 activating biological channels, is it possible to create some sort of drug that halts all LMP1 processes in the hopes that the Epstein-Barr virus will not be able to continue transforming cells into tumor cells? Is it possible for the immune system to enter the exosome pathways in order to stop the EBV from further spreading?