Vascular endothelial growth factor/vascular permeability factor in the pathogenesis of primary effusion lymphomas.

Abstract

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.

• Authors: Y Aoki, G Tosato
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 41 Issue 3-4 Pg. 229-37 (Apr 2001) ISSN: 1042-8194 [Print] United States
• PMID: 11378536 (Publication Type: Journal Article, Review)

Chemical References

• Endothelial Growth Factors
• Lymphokines
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors

Topics

• Animals
• Endothelial Growth Factors (adverse effects, metabolism, physiology)
• Herpesviridae Infections (complications)
• Herpesvirus 8, Human
• Humans
• Lymphokines (adverse effects, metabolism, physiology)
• Lymphoma, AIDS-Related (etiology, metabolism)
• Peritoneal Neoplasms (etiology, metabolism)
• Pleural Effusion, Malignant (etiology, metabolism)
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors