Vascular endothelial growth factor/vascular permeability factor in the pathogenesis of primary effusion lymphomas.
Primary effusion lymphomas (PEL), rare lymphomas associated with Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) infection, present as malignant lymphomatous effusions in body cavities. We have recently found that PEL effusions contain high levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). VEGF/VPF, an important regulator of tumor-angiogenesis in vivo, exerts its effects acting through the receptors KDR/Flk-1 and Flt-1 on the endothelial cell membrane. In vitro, the PEL cell lines BC-1, BCP-1 and BCBL-1 produce high levels of VEGF. RT-PCR analysis of RNA from the PEL cell lines amplified the three VEGF/VPF secreted isoforms, VEGF/VPF(121), VEGF/VPF(145) and VEGF/VPF(165). Two of the PEL cell lines express the VEGF/VPF receptor Flt-1, but VEGF did not stimulate proliferation in these cells. SCID/beige mice inoculated intraperitoneally with BCBL-1 cells developed effusion lymphoma of human cell origin with prominent bloody ascites. In contrast, none of the mice treated with a neutralizing anti-human VEGF/VPF antibody developed ascites and effusion lymphoma. Although the precise mechanisms by which VEGF/VPF can promote vascular permeability are not fully understood, VEGF/VPF stimulation of vascular leakage may be critical to the pathogenesis of PEL.
Aoki
Y
Y
Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. aokiy@mail.nih.gov
Tosato
G
G
D000818:Animals; D016228:Endothelial Growth Factors / Q000009:adverse effects / Q000378:metabolism / Q000502:physiology*; D006566:Herpesviridae Infections / Q000150:complications; D019288:Herpesvirus 8, Human; D006801:Humans; D008222:Lymphokines / Q000009:adverse effects / Q000378:metabolism / Q000502:physiology*; D016483:Lymphoma, AIDS-Related / Q000209:etiology* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000209:etiology / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000209:etiology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors