Epstein-Barr Virus Latent Membrane Protein 1 Induces Cancer Stem/Progenitor-Like Cells in Nasopharyngeal Epithelial Cell Lines

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Abstract
Recent studies suggest the existence of cancer stem cells (CSC) and cancer progenitor cells (CPC), although strict definitions of neither CSC nor CPC have been developed. We have produced evidence that the principal oncoprotein of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), which is associated with human malignancies, especially nasopharyngeal carcinoma (NPC), promotes tumor cell invasion and metastasis, as well as the epithelial-mesenchymal transition (EMT). However, whether LMP1 is involved in the development of CSC/CPC is still unclear. This study investigates whether the expression of EBV-LMP1 is related to the development of CSC/CPC. Analysis of cancer stem cell markers reveals that LMP1 induces the CD44high CD24low CSC/CPC-like phenotype as well as self-renewal abilities in LMP1-expressing epithelial cell lines. In addition, we show here that LMP1 induction in epithelial cells causes high tumorigenicity and rapid cellular proliferation. Furthermore, we found that LMP1 expression increased the expression of several CPC markers as well as producing increased levels of EMT markers. Our findings indicate that LMP1 can induce a CPC-like rather than a CSC-like phenotype in epithelial cells and suggest that LMP1-induced phenotypic changes contribute to the development of NPC.

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