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

Abstract

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.

Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo

“…We next examined the expression of the VEGF receptors, VEGFR1 and VEGFR2. Consistent with the results of a previous report, 19 the OGU1 cell line expressed VEGFR1 mRNA and a much lower level of VEGFR2 mRNA, but these transcripts were not detectable in other cell lines (Figure 2C ). VEGFR1 and VEGFR2 proteins were not detected by flow cytometry on the cell surface of these four HHV8‐unrelated ELBCL cell lines (data not shown).…”

“…To the best of our knowledge, to date, only three HHV8‐unrelated ELBCL cell lines, STR‐428, OGU1 and Pell‐1, all of which were derived from Japanese patients, have been characterized in detail. 17 , 18 , 19 Using these HHV8‐unrelated ELBCL cell lines together with a newly established Pell‐2 cell line, we assessed for the first time the role of VEGF in lymphomagenesis both in vitro and in vivo, and efficacy of a VEGF‐targeted strategy for this neoplasm. We found two different VEGF secretion patterns by HHV8‐unrelated ELBCL cells in vitro.…”

“…STR‐428 and OGU1 were obtained from the Japanese Collection of Research Bioresources and Riken BioResource Research Center, respectively. 18 , 19 Optimal conditions for the growth of these cell lines were RPMI 1640 medium supplemented with 10% FBS at 37°C in a humidified atmosphere of 5% CO 2 in air. The detailed characteristics of Pell‐1 are described elsewhere.…”

“…Four HHV8‐unrelated ELBCL cell lines, STR‐428, OGU1, Pell‐1 and Pell‐2, were used in this study. STR‐428 and OGU1 were obtained from the Japanese Collection of Research Bioresources and Riken BioResource Research Center, respectively 18,19 . Optimal conditions for the growth of these cell lines were RPMI 1640 medium supplemented with 10% FBS at 37°C in a humidified atmosphere of 5% CO 2 in air.…”

Development of a novel cell line‐derived xenograft model of primary herpesvirus 8‐unrelated effusion large B‐cell lymphoma and antitumor activity of birabresib in vitro and in vivo

“…Cell lines provide invaluable tools for research on rare diseases, by which unlimited supplies of tumor cells can be studied repeatedly and extensively. Although numerous HHV8‐positive PEL cell lines have been reported, 16,17 only a few lines derived from HHV8‐unrelated primary lymphomatous effusions have been reported 18,19 . However, most of these cell lines have not been authenticated genetically against the primary tumor.…”