Vascular permeability factor (VPF), also known as
vascular endothelial growth factor (
VEGF), plays an important role in the angiogenesis associated with the growth of many human and animal
tumors. VPF/
VEGF stimulates endothelial cell growth and increases microvascular permeability by interacting with two endothelial cell
tyrosine kinase receptors, KDR and flt-1. We studied 16 cases of
AIDS-associated
Kaposi's sarcoma (KS), 2 cases of cutaneous
angiosarcoma, and 6 cases of
capillary hemangioma by in situ hybridization for expression of VPF/
VEGF, KDR, and flt-1 mRNAs. We also performed immunohistochemical staining for VPF/
VEGF protein in 15 cases.
Tumor cells in KS and
angiosarcoma strongly expressed KDR but not flt-1
mRNA. Endothelial cells in small stromal vessels in and around these
tumors strongly expressed both KDR and flt-1 mRNAs.
Tumor cells expressed VPF/
VEGF mRNA strongly in only one case of KS, adjacent to an area of
necrosis. This was also the only case in which the
tumor cells stained substantially for VPF/
VEGF protein. VPF/
VEGF mRNA and
protein were, however, strongly expressed by squamous epithelium in areas of
hyperplasia and near areas of ulceration overlying
tumors. VPF/
VEGF mRNA was also expressed focally at lower levels by infiltrating inflammatory cells, probably macrophages. The strong expression of both KDR and flt-1 in small stromal vessels in and around
tumors suggests that VPF/
VEGF may be an important regulator of the
edema and angiogenesis seen in these
tumors. The strong expression of KDR by
tumor cells in KS and
angiosarcoma implies that VPF/
VEGF may also have a direct effect on
tumor cells.
Tumor cells in four of six
capillary hemangiomas strongly expressed both KDR and flt-1 mRNAs in contrast to the high level expression of only KDR observed in the malignant vascular
tumors studied. Neither VPF/
VEGF mRNA or
protein were strongly expressed in
capillary hemangiomas. VPF/
VEGF and its receptors may play an important but as yet incompletely understood role in the pathogenesis of both benign and malignant vascular
tumors.