OGU1: Novel VEGF-producing HHV-8-unrelated PEL-like lymphoma cell line

Under immunocompromised conditions such as human immunodeficiency virus (HIV) infection, human herpesvirus-8 (HHV-8) is associated with the development extracavitary large B-cell lymphoma, a condition known as primary effusion lymphoma (PEL). Recently, body cavity-based lymphomas have emerged that resemble PEL, but are not associated with HHV-8 and develop in the absence of HIV infection; these have been termed HHV-8-unrelated PEL-like lymphoma. HHV-8-unrelated PEL-like lymphomas show distinct features from PEL, including expression of pan-B cell markers, frequent occurrence in elderly patients, and a more favorable response to therapy. However, this type of lymphoma also shows some heterogeneity with respect to its clinical manifestation, and its pathophysiology is largely unknown. To elucidate the oncogenetic mechanism of this type of lymphoma, we established and characterized a novel cell line, named OGU1, from a patient with HHV-8-unrelated PEL-like lymphoma with ascites development.

OGU1 cells expressed CD20 and CD19 pan-B cell markers and revealed a rearrangement of the immunoglobulin heavy chain gene identical to the parental tumor cells. HHV-8 mRNA and its encoded product LANA-1 were not detected in either OGU1 cells or the parental tumors, which is compatible with the typical features of HHV-8-unrelated PEL-like lymphoma. Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of a variety of tumors, including hematologic malignancies, and has been reported as a useful marker for predicting the prognosis of non-Hodgkin’s lymphomas. We found that the OGU1 cells produced abundant VEGF and expressed VEGF receptor-1 at both the mRNA and protein levels. Intriguingly, monoclonal antibodies against VEGF or inhibitors for the VEGF receptor caused growth retardation of the cells, indicating that VEGF, at least in part, promotes the proliferation or survival of OGU1 cells thorough an autocrine mechanism. Furthermore, we found activation of tyrosine kinases (Src and Lyn), PKCa, and S6K1 signaling molecules, and high expression levels of miRNAs such as the miR-17-92 cluster, suggesting a role of these molecules in the lymphomagenesis of the cells.