Vascular permeability factor (VPF, VEGF) in tumor biology

Abstract

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine expressed and secreted at high levels by many tumor cells of animal and human origin. As secreted by tumor cells, VPF/VEGF is a 34-42 kDa heparin-binding, dimeric, disulfide-bonded glycoprotein that acts directly on endothelial cells (EC) by way of specific receptors to activate phospholipase C and induce [Ca2+]i transients. Two high affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described. VPF/VEGF is likely to have a number of important roles in tumor biology related, but not limited to, the process of tumor angiogenesis. As a potent permeability factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin deposition which alters the tumor extracellular matrix. This matrix promotes the ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF is a selective endothelial cell (EC) growth factor in vitro, and it presumably stimulates EC proliferation in vivo. Furthermore, VPF/VEGF has been found in animal and human tumor effusions by immunoassay and by functional assays and very likely accounts for the induction of malignant ascites. In addition to its role in tumors, VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation. VPF/VEGF is expressed in normal development and in certain normal adult organs, notably kidney, heart, adrenal gland and lung. Its functions in normal adult tissues are under investigation.

Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer

“…The issue of methodological consistency, such as how to sample the heterogeneous cancer, which antibody to use, and how to assess or count the vessels, may hamper the development of vessel density into an established prognostic indicator. The role of angiogenic factors, such as VEGF, that stimulate the formation of new blood vessels, has been well established (33). Since angiogenesis is essential for the growth, invasion, and metastasis of cancers, the stimulatory factors may also serve as prognostic factors.…”

Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in human melanoma

“…The neovascularization and growth of experimental tumours can be inhibited by treatment with monoclonal antibodies against VEGF (Kim et al, 1993;Asano et al, 1995;Melnyk et al, 1996). Finally, VEGF increases microvascular permeability to macromolecules, thereby leading to fibrinogen extravasation and fibrin deposition, which are important processes in tumour angiogenesis (Senger et al, 1993).…”

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

“…For the s.c. model, tumor size was determined by the formula L(W 2 )/2, with measurements being taken in mm with digital calipers. This yielded tumor volume in mm 3 , which we have determined to be roughly equivalent to tumor weight in grams. When tumors reached a size of between 0.5 and 1 g, the animals were terminated, and tumors collected in formalin.…”

“…Several studies have demonstrated, for example, that an increase in cytosolic levels of vascular endothelial growth factor (VEGF) in tumor tissue samples is indicative of poorer prognosis for patients with node-negative breast carcinoma. 1,2 VEGF plays a key role in the process of angiogenesis, 3 and the extent of tumor angiogenesis is now widely accepted as a prognostic factor in several cancer types, [4][5][6][7][8] with higher levels being indicative of more aggressive disease.…”