INDUCTION OF CD44 EXPRESSION BY THE EPSTEIN-BARR-VIRUS LATENT MEMBRANE-PROTEIN LMP1 IS ASSOCIATED WITH LYMPHOMA DISSEMINATION

Epstein-Barr Virus (EBV) is implicated in the pathogenesis of endemic Burkitt's lymphoma (BL), B-cell lymphomas occuring 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 EBNA1 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 ave 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 1 (LMP1) gene. Introduction of LMP1 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 LMP1-/CD44-BL cells was observed to confer the disseminated tumor growth pattern associated with LMPI expression. Taken together our results show that expression of LMP1 may regulate expression of CD44 and play an important role in the behavior of EBV-based lymphomas. (C) 1995 Wiley-Liss, Inc.