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Establishment and characterization of a novel VEGF-producing HHV-8-unrelated PEL-like lymphoma cell line, OGU1

Significance Statement

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. OGU1 cells may be a useful model for investigating the tumor biology of this unique type of lymphoma.  

FigureLegend: OGU1 cells were negative for HHV-8 (immunostaining with anti-HHV-8 antibody, left panel).

VEGF mRNA expression in OGU1 cell line was detected by RT-PCR (right panel). Arrow indicates VEGF mRNA. S; sample (OGU1), PC; positive control, NC; normal control, MQ; Milli-Q, M; size marker.

Establishment and characterization of a novel VEGF-producing HHV-8-unrelated PEL-like lymphoma cell line,OGU1. Global Medical Discovery

About The Author

Kiyotaka Kawauchi completed his residency in internal medicine at Tokyo Women’s Medical University Daini Hospital, and then proceeded to a specialty in hematology and oncology. He received a Ph.D in medicine from Tokyo Women’s Medical University in 1988, in which he studied the mechanism of interferon-induced human natural killer cell activation. He also conducted research on B-cell antigen receptor signaling at the Best Institute of the University of Toronto in Canada from 1991 to 1994 as a postdoctoral fellow. He obtained the position of Associate professor at Tokyo Women’s Medical University Medical Center East in 1999. He is now a director of the Nishiogu Clinic. He also serves as a councilor of the Japanese Society of Hematology and is a member of the editorial board of Case Reports in Hematology.  

Journal Reference

Eur J Haematol. 2016 Feb;96(2):144-51.

Kawauchi K1,2, Ogasawara T1, Aiba M3, Fujibayashi M3, Sanaka T4, Sakura H1, Shibuya M5,6.

Show Affiliations
  1. Medical Center East, Department of Medicine, Tokyo Women’s Medical University, Tokyo, Japan.
  2. Nishiogu Clinic, Tokyo, Japan.
  3. Medical Center East, Department of Surgical Pathology, Tokyo Women’s Medical University, Tokyo, Japan.
  4. Center of CKD and Lifestyle Related Diseases, Edogawa Hospital, Ichikawa city, Japan.
  5. Institute of Physiology and Medicine, Jobu University, Takasaki, Japan.
  6. Institute of Medical Science, University of Tokyo, Tokyo, Japan. 


Primary effusion lymphoma (PEL) is a rare B-cell lymphoma subtype that is characterized by lymphomatous effusion without the presence of masses, and it typically occurs in human immunodeficiency virus (HIV)-infected individuals. Lymphoma cells are universally positive for human herpesvirus 8 (HHV-8). Recently, a cavity-based effusion lymphoma that is similar to PEL without HHV-8 infection, called HHV-8-unrelated PEL-like lymphoma, has been reported in non-HIV-infected individuals. However, the pathophysiology of this lymphoma is largely undefined. We established a novel B-cell line OGU1 derived from a patient with HHV-8-unrelated PEL-like lymphoma. Notably, OGU1 cells produced vascular endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors retarded cell growth. Because VEGF acts as a vascular permeability and growth factor, it could play a role, at least in part, in the pathogenesis of this unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV-8-unrelated PEL-like lymphoma.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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