Induction of CD44 expression by the epstein‐barr virus latent membrane protein LMP1 is associated with lymphoma dissemination

Abstract

Epstein-Barr Virus (EBV) is implicated in the pathogenesis of endemic Burkitt's lymphoma (BL), B-cell lymphomas occurring under immunosuppression, nasopharyngeal carcinoma and Hodgkin's disease. Two distinct patterns of latent EBV gene expression occur in EBV-associated lymphomas. BLs typically display expression of the nuclear antigen EBNAI only, whereas EBV-associated, non-Burkitt B-cell lymphomas express at least 9 latent viral genes (6 EBNAs and 3 latent membrane proteins), reminiscent of in vitro EBV-immortalized lymphoblastoid cell lines (LCL). BLs are characterized by local, extra-nodal growth, whereas EBV-associated B-cell lymphomas often disseminate to peripheral lymphoid tissue. We show here that BL cells forming local tumors after xenotransplantation into SCID mice disseminate to lymphoid tissue following introduction of the latent membrane protein I (LMP 1) gene. Introduction of LMP 1 into BL cells induced expression of CD44 on the cell surface, a molecule implicated in enhanced lymphoid tumor growth and dissemination. Introduction of CD44 into LMP 1-/CD44-BL cells was observed to confer the disseminated tumor growth pattern associated with LMP 1 expression. Taken together our results show that expression of LMP 1 may regulate expression of CD44 and play an important role in the behavior of EBV-based lymphomas.

Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration

“…To look for potential binding candidates for ezrin, we evaluated which membrane-anchored cell-adhesion molecule binds phosphorylated ezrin. LMP1 is reported to be associated with ICAM-1 and CD44 (Walter et al ., 1995; Park et al ., 2002). Fig.…”

Epstein-Barr Virus LMP1 Modulates Lipid Raft Microdomains and the Vimentin Cytoskeleton for Signal Transduction and Transformation

“…Interestingly, LMP1 expression results in the induction of cell surface molecules and the activation of signaling pathways that contribute to cell attachment, migration, and invasion (49)(50)(51). The molecular mechanisms driving many of these changes are still unclear, but transcriptional upregulation by LMP1 clearly contributes.…”

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus

“…This correlation was independent of other pathologic factors, since factors such as lymph node metastasis and lymphatic invasion were not significantly different between EBVaGC and EBV-negative carcinomas (Table III). There have been several observations regarding CD44-expression in EBV-associated malignancies (Wang et al, 1990;Walter et al, 1995;Brooks et al, 1995). The EBV-encoded latent membrane protein-1, LMP1, has been shown to upregulate the standard form of CD44 expression when it is introduced into lymphoma cell lines, such as Daudi or Burkitt lymphoma cells (Wang et al, 1990;Walter et al, 1995).…”

“…There have been several observations regarding CD44-expression in EBV-associated malignancies (Wang et al, 1990;Walter et al, 1995;Brooks et al, 1995). The EBV-encoded latent membrane protein-1, LMP1, has been shown to upregulate the standard form of CD44 expression when it is introduced into lymphoma cell lines, such as Daudi or Burkitt lymphoma cells (Wang et al, 1990;Walter et al, 1995). On the other hand, immunohistochemical evaluation of both LMP1 and CD44 variants in nasopharyngeal carcinoma tissues demonstrated that there was no correlation between the expression of the 2 molecules (Brooks et al, 1995).…”