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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4247-4254
Role of Vascular Endothelial Growth Factor/Vascular Permeability
Factor in the Pathogenesis of Kaposi's Sarcoma-Associated
Herpesvirus-Infected Primary Effusion Lymphomas
Yoshiyasu Aoki and
Giovanna Tosato
From the Division of Hematologic Products, Center for Biologics
Evaluation and Research, Food and Drug Administration, Bethesda, MD.
Primary effusion lymphomas (PELs), which are rare lymphomas
associated with Kaposi's sarcoma-associated herpesvirus (or human herpesvirus-8) infection, present as malignant lymphomatous effusions in body cavities. Because PELs prefer liquid growth, we hypothesized that increased vascular permeability would be required for effusions to
form. We found that the PEL cell lines BC-1, BCP-1, and BCBL-1 produce
high levels of vascular endothelial growth factor/vascular permeability
factor (VEGF/VPF). Reverse transcriptase-polymerase chain reaction
analysis of RNA from the PEL cell lines amplified the 3 VEGF-secreted
isoforms: VEGF/VPF121, VEGF/VPF145, and
VEGF/VPF165. Two of the PEL cell lines expressed the
VEGF/VPF receptor Flt-1, but VEGF/VPF did not stimulate proliferation
in these cells. Most (13/14) control SCID/beige mice inoculated
intraperitoneally with BCBL-1 cells and subsequently observed or
treated with control antibodies developed effusion lymphoma of human
cell origin with prominent bloody ascites. In contrast, none (0/9) of
the mice treated with a neutralizing antihuman VEGF/VPF antibody
developed ascites and effusion lymphoma. These results demonstrate that VEGF/VPF is critical to BCBL-1 growth as effusion lymphoma in mice and
suggest that VEGF/VPF stimulation of vascular permeability may be
critical to the pathogenesis of PELs.
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