Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.

Abstract

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), increases microvascular permeability and is a specific mitogen for endothelial cells. Expression of VPF/VEGF previously was demonstrated in a variety of tumor cells, in cultures of pituitary-derived cells, and in corpus luteum. Here we present evidence, by Northern analysis and in situ hybridization, that the VPF/VEGF gene is expressed in many adult organs, including lung, kidney, adrenal gland, heart, liver, and stomach mucosa, as well as in elicited peritoneal macrophages. The highest levels of VPF/VEGF transcripts were found in epithelial cells of lung alveoli, renal glomeruli and adrenal cortex, and in cardiac myocytes. The prominence of VPF/VEGF mRNA in these tissues suggests a possible role for VPF/VEGF in regulating baseline microvascular permeability, which is essential for tissue nutrition and waste removal. We also demonstrate particularly high VPF/VEGF mRNA levels in several human tumors, where it may be involved in promoting tumor angiogenesis and stroma generation, both as an endothelial cell mitogen and indirectly by its permeability enhancing effect that leads to the deposition of a provisional fibrin gel matrix.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells

“…Perhaps. VPF/VEGF is strongly expressed by a number of di erent normal cells and tissues in adults in the absence of detectable angiogenesis (Berse et al, 1992). As a consequence, low levels of VPF/VEGF are found in normal plasma (Yamamoto et al, 1996), despite an extremely low level of endothelial cell turnover in adults (Engerman et al, 1967).…”

Concurrent Induction of Lymphangiogenesis, Angiogenesis, and Macrophage Recruitment by Vascular Endothelial Growth Factor-C in Melanoma

“…The probe for human VEGF hybridizes with a region of VEGF mRNA common to all known VEGF splice variants. 37 A human ␤-actin cDNA probe (Clontech, Palo Alto, CA) was used as a control for equal RNA loading. Blots were hybridized at 65°C for 24 hours, washed at high stringency, and exposed to X-OMAT MR film (Kodak, Rochester, NY).…”

The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells

“…Another explanation involves an increase in the availability of VEGF sequestered in the extracellular matrix (ECM) due to the action of a matrix metalloproteinase (MMP) that is concomitantly upregulated during carcinogenesis (Bergers et al, 2000). However, the mechanism by which vascular quiescence is maintained in normal tissues, wherein VEGF is widely expressed (Berse et al, 1992;Hanahan and Folkman, 1996), remains unclear. Several secreted proteins have been reported to bind and sequester VEGF (Kendall and Thomas, 1993;Gengrinovitch et al, 1995;Gupta et al, 1999;Inoki et al, 2002;Luque et al, 2003).…”

“…In tumors, stromal fibroblasts as well as cancer cells are a significant source of VEGF promoting angiogenesis (Hlatky et al, 1994;Fukumura et al, 1998;Dong et al, 2004). Although the phenotypic changes in tumor fibroblasts are considered responsible for the angiogenic properties as distinct from those of normal fibroblasts (Orimo et al, 2005;Kalluri and Zeisberg, 2006), fibroblasts from normal tissues also produce VEGF (Berse et al, 1992;Hlatky et al, 1994). This suggests that a mechanism other than the regulation of VEGF expression may modulate fibroblast VEGF activity, and subsequently affect whether angiogenesis is triggered in those tissues.…”