Differential tumorigenicity between Epstein-Barr virus genome-positive and genome-negative cell lines with t(11;14)(q13;q32) derived from mantle cell lymphoma

Abstract

Epstein-Barr virus (EBV) genome has been detected in several human lymphoproliferative diseases, but the oncogenic function of EBV is not fully understood. We previously established EBV-positive (SP-50B) and EBV-negative (SP-53) cell lines with the t(11;14)(q13;q32) chromosome abnormality from a single patient with mantle cell lymphoma. Monoclonal EBV DNA in a circular episomal form was demonstrated in the SP-50B cells by Southern blot hybridization with the EBV-terminal fragment probe. SP-50B cells were positive for not only EBV-encoded nuclear antigen-1 (EBNA1) but also latent membrane protein-1 and EBNA2. None of the EBV-encoded proteins was expressed in SP-53 cells. The isogenic EBV-infected and EBV-free cell lines of neoplastic clones made it possible to examine a tumorigenic role of EBV. Only EBV-positive SP-50B cells possessed malignant phenotypes, such as growth ability in low serum, colony formation in soft agarose, and tumorigenicity in nude mice. On the other hand, a lymphoblastoid B-cell line established by infecting the patient's normal B lymphocytes in vitro with exogenous EBV had no tumorigenicity. These results suggested that EBV infection, if it occurred in neoplastic lymphoma cells, could play a role in acquisition of malignant phenotypes.