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Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker.

Niers TM, Richel DJ, Meijers JC, Schlingemann RO - PLoS ONE (2011)

Bottom Line: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer.Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated.This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis.

Methodology: We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC) and 12 patients with renal cell carcinoma (RCC). In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6), non-RCC: 6.2 IU/10(6) platelets, p = 0.001). In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001), and not related to platelet VEGF concentration.

Conclusions: Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cancer.

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Scatter plot presentation of the distribution of β-TG and PF4.A) β-TG and PF4 measured in PECT plasma of cancer patients compared to controls. B) β-TG and PF4 measured in platelets of cancer patients compared to controls. Bars represent the medians.
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pone-0019873-g003: Scatter plot presentation of the distribution of β-TG and PF4.A) β-TG and PF4 measured in PECT plasma of cancer patients compared to controls. B) β-TG and PF4 measured in platelets of cancer patients compared to controls. Bars represent the medians.

Mentions: In PECT plasma, we found two-fold higher PF4 values in cancer patients compared to healthy controls. This indicates that platelets from cancer patients are more prone to become activated. However, an increased PF4 concentration in individual platelets of cancer patients may also have contributed to the increased PF4 concentration in PECT plasma (Figure 3).


Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker.

Niers TM, Richel DJ, Meijers JC, Schlingemann RO - PLoS ONE (2011)

Scatter plot presentation of the distribution of β-TG and PF4.A) β-TG and PF4 measured in PECT plasma of cancer patients compared to controls. B) β-TG and PF4 measured in platelets of cancer patients compared to controls. Bars represent the medians.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102663&req=5

pone-0019873-g003: Scatter plot presentation of the distribution of β-TG and PF4.A) β-TG and PF4 measured in PECT plasma of cancer patients compared to controls. B) β-TG and PF4 measured in platelets of cancer patients compared to controls. Bars represent the medians.
Mentions: In PECT plasma, we found two-fold higher PF4 values in cancer patients compared to healthy controls. This indicates that platelets from cancer patients are more prone to become activated. However, an increased PF4 concentration in individual platelets of cancer patients may also have contributed to the increased PF4 concentration in PECT plasma (Figure 3).

Bottom Line: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer.Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated.This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis.

Methodology: We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC) and 12 patients with renal cell carcinoma (RCC). In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6), non-RCC: 6.2 IU/10(6) platelets, p = 0.001). In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001), and not related to platelet VEGF concentration.

Conclusions: Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cancer.

Show MeSH
Related in: MedlinePlus