Human tumor virus utilizes exosomes for intercellular communication.
The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is expressed in multiple human malignancies and has potent effects on cell growth. It has been detected in exosomes and shown to inhibit immune function. Exosomes are small secreted cellular vesicles that contain proteins, mRNAs, and microRNAs (miRNAs). When produced by malignant cells, they can promote angiogenesis, cell proliferation, tumor-cell invasion, and immune evasion. In this study, exosomes released from nasopharyngeal carcinoma (NPC) cells harboring latent EBV were shown to contain LMP1, signal transduction molecules, and virus-encoded miRNAs. Exposure to these NPC exosomes activated the ERK and AKT signaling pathways in the recipient cells. Interestingly, NPC exosomes also contained viral miRNAs, several of which were enriched in comparison with their intracellular levels. LMP1 induces expression of the EGF receptor in an EBV-negative epithelial cell line, and exosomes produced by these cells also contain high levels of EGF receptor in exosomes. These findings suggest that the effects of EBV and LMP1 on cellular expression also modulate exosome content and properties. The exosomes may manipulate the tumor microenvironment to influence the growth of neighboring cells through the intercellular transfer of LMP1, signaling molecules, and viral miRNAs.
The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
David G
DG
Meckes
Kathy H Y
KH
Shair
Aron R
AR
Marquitz
Che-Pei
CP
Kung
Rachel H
RH
Edwards
Nancy
N
Raab-Traub
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002277:Carcinoma; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism / Q000821:virology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000821:virology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases