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

Leuk Lymphoma. 2001 Apr;41(3-4):229-37. doi: 10.3109/10428190109057978.

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.

Publication types

  • Review

MeSH terms

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

Substances

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