Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients

Beerepoot, Laurens V.; Mehra, Niven; Vermaat, Joost S.P.; Zonnenberg, Bernard A.; Gebbink, M. F. G. B.; Voest, Emile E.

doi:10.1093/annonc/mdh017

Cited by 232 publications

(236 citation statements)

References 41 publications

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“…In concordance to literature our comparison of controls and newly diagnosed breast cancer patients showed increased numbers of CEC in the cancer patients with both methods (Mancuso et al, 2001;Beerepoot et al, 2004). In real-time PCR the difference was more pronounced as in the flow cytometric detection.…”

Section: Discussionsupporting

confidence: 90%

“…Unfortunately, clinical markers to assess neoangiogenesis in patients or the response to antiangiogenic treatment are still scanty. Circulating endothelial cell numbers in peripheral blood seem to be a relevant marker of neoangiogenesis since CEC are elevated in cancer patients and the amounts of CEC correlates with progressive disease (Mancuso et al, 2001;Beerepoot et al, 2004). The amounts of CEC in peripheral blood can be measured by flow cytometry, but this requires fresh blood samples and a complex four-colour analysis with the acquisition of many events.…”

Section: Discussionmentioning

confidence: 99%

“…An increase of circulating endothelial cells (CEC) is described in several pathologic conditions that involve vascular injury or instability as myocardial infarction, infectious vasculitis and cancer (Mutin et al, 1999;Mancuso et al, 2001;Woywodt et al, 2003;Beerepoot et al, 2004). These CEC are mostly viable and exhibit still proliferative capacity despite their terminal differentiation (Lin et al, 2000;Mancuso et al, 2001;Ribatti, 2004).…”

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confidence: 99%

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Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis

et al. 2005

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Angiogenesis is a fundamental process in tumour growth and metastatic dissemination. Possible surrogate markers for tumour angiogenesis are the amounts of circulating endothelial cells (CEC) in peripheral blood and the plasma concentration of vascular endothelial growth factor (VEGF). We tested the suitability of real-time PCR for CD146, an endothelial cell-specific antigen, to quantify CEC numbers in comparison to a flow cytometry quantification. Real-time PCR of CD146 mRNA showed high sensitivity and linearity for the quantification of cultivated primary endothelial cells added in different amounts to blood samples. Circulating endothelial cell numbers were quantified in peripheral blood samples of breast cancer patients and healthy controls by four-colour flow cytometry analysis and CD146 real-time PCR, and VEGF plasma concentrations were measured by ELISA. The amounts of CEC detected with both methods correlated significantly and CEC numbers were significantly increased in newly diagnosed breast cancer patients compared to healthy controls. Vascular endothelial growth factor concentrations correlated significantly with CEC numbers, but there was no significant difference in VEGF levels between breast cancer patients and healthy controls indicating that VEGF plasma levels cannot be used as surrogate marker for tumour angiogenesis. Taken together, the quantification of CEC by CD146 realtime PCR showed equivalent results to the flow cytometry analysis. Thus, CD146 real-time PCR may be an easy and reliable approach to quantify CEC in peripheral blood samples and could facilitate the integration of CEC measurements in clinical studies exploring the efficacy of antiangiogenic therapies.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis

et al. 2005

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“…In addition, Kaplan et al (2005) reported that bone marrow-derived HPCs express VEGFR1 home to tumour-specific premetastatic sites, and form cellular clusters that provide a permissive niche for incoming tumour cells before the arrival of tumour cells. Another possible source may be mature vessel-derived endothelial cells, which might be the largest source of VEGFR1-expressing circulating endothelial cells (CECs) (Mancuso et al, 2001;Beerepoot et al, 2004). Contrary to our expectation, there was no significant difference in the number of VEGFR1-expressing cells of CD133 þ /À CD31 þ Figure 1 VEGFR1 mRNA expression in peripheral blood from gastric cancer cases.…”

Section: Discussionmentioning

confidence: 81%

Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood

et al. 2007

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Identification of an isolated tumour cell with metastatic ability is important for predicting the recurrence and prognosis of gastric cancer. A biological marker for evaluating the metastatic ability of gastric cancer cells has not yet been identified. We assessed vascular endothelial growth factor receptor-1 mRNA expression by quantitative real-time reverse transcriptase-polymerase chain reaction. Vascular endothelial growth factor receptor-1 mRNA in peripheral blood was more highly expressed in perioperative metastasis-positive and postoperative recurrence cases than in normal control cases, early cancer cases and nonmetastatic advanced cancer cases. The peripheral blood vascular endothelial growth factor receptor-1 mRNA-positive group was associated with advanced clinical stage, deep invasion beyond the muscularis propria, lymphatic involvement, vascular involvement, lymph node metastasis, positive peritoneal lavage cytology, preoperative metastasis and postoperative recurrence. Flow cytometry analysis disclosed that vascular endothelial growth factor receptor-1 expressing cells in the peripheral blood were more abundant in cancer cases with metastases than in cases without metastases. Our data suggest that the amount of positive cells may provide information on the clinical features of gastric cancer, especially in regard to gastric cancer metastasis.

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“…Since several new antitumor drugs target tumor angiogenesis or tumor vasculature, CEC counts are a potential surrogate marker for assessing drug efficiency and therefore hold promise to avoid over-or undertreatment of individual patients. In addition, reductions in CEC concentrations may reflect tumor growth and thereby serve as a parameter to reveal disease progression at an early stage (9).…”

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confidence: 99%

Cells meeting our immunophenotypic criteria of endothelial cells are large platelets

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et al. 2007

Cytometry Part B Clinical

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Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients

Abstract: In progressive cancer patients, the amount of CECs is increased. These CECs are viable and may contribute to vessel formation. The number of CECs is influenced by anticancer treatment.

Cited by 232 publications

References 41 publications

Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis

Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis

Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood

Cells meeting our immunophenotypic criteria of endothelial cells are large platelets

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