Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer

Abstract

Vascular endothelial growth factor (VEGF) is a major target for the inhibition of tumour vascularisation and the treatment of human cancer. Many tumours produce large quantities of VEGF, and as a result, diagnosis and prognosis of cancer may be predicted by measuring changes in VEGF concentrations in blood. In blood, the VEGF may be located in the plasma, or in the blood-borne cells and formed elements, in particular, platelets and leukocytes. In this study, we collate the measurements of VEGF in platelets, leukocytes, plasma and serum for breast, prostate, colorectal and other cancers. In addition, we analysed the concentration of VEGF in tumour tissue itself, as well as for other tissues in the human body. Although the concentration of VEGF in tumours is high, the size of tumours is small compared to other tissues, in particular, skeletal muscle. Thus, the total quantity of VEGF in tumours and in blood is small compared to the quantity in muscles. This large reservoir of VEGF may have important implications for the treatment of cancer.

Normal ranges of angiogenesis regulatory proteins in human platelets

“…We found no direct measurement data on platelet levels of PF4 in the literature for comparison. A review by Kut et al [26] reports plasma VEGF to fall between 19 ± 8 and 47 ± 8 pg/mL. These values, generated from a variety of methods, were similar to our average value of 46 ± 18 pg/mL.…”

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

“…We examined kinase activation in endothelial cells stimulated by VEGF and 5-HT simultaneously under identical experimental conditions. In healthy human subjects, the mean levels of VEGF were 42 pg/mL in plasma and 173 pg/mL in serum [30]. However, VEGF above its human serum concentration (200 pg/mL) could not stimulate kinase activation in endothelial cells (data not shown).…”

Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In vitro

“…Serum was immediately stored at −80°C and kept frozen until analysis. Debate exists on the most accurate analysis of VEGF levels, serum versus plasma, because VEGF has been shown to be released from platelets on serum preparation (26). Serum was chosen in this study for several reasons, including the observation that platelets may be involved in tumor metastasis and reflect the biology of cancer, and therefore platelet-derived VEGF may reflect the biology of cancer (34).…”

“…It has been reported that higher levels of VEGF are present in the serum and plasma of men with prostate cancer compared with healthy controls, and increased VEGF levels are associated with metastatic disease and biochemical progression (24,25). A recent meta-analysis has shown that VEGF levels in serum or plasma are ∼2.18 and 1.85 times greater (weighted average of all cancer studies analyzed), respectively, in prostate cancer patients versus healthy controls (26). Finally, HGF and VEGF levels have been found in some studies to increase early during tumorigenesis (27)(28)(29)(30)(31), suggesting that the use of natural compounds that can block the HGF/c-Met, VEGF, and/or IGF-I signaling axis may show promise both as chemopreventive agents and as anticancer agents slowing the progression of established tumors.…”