title: Epstein-Barr virus latent membrane protein 1 induces cancer stem/progenitor-like cells in nasopharyngeal epithelial cell lines.
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 CD44(high) CD24(low) 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.
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Pagano
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D051927:CD24 Antigen / Q000096:biosynthesis*; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D013234:Stem Cells / Q000821:virology*; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018960:Hyaluronan Receptors; D009856:Oncogene Proteins, Viral; D014763:Viral Matrix Proteins