High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer

Krisztina Bogos, Ferenc Renyi-Vamos, J. Dobos, I. Kenessey, J. Tóvári, J. Tímár, J. Strausz, G. Ostoros, Walter Klepetko, Hendrik Jan Ankersmit, Gyorgy Lang, Mir Alireza Hoda, Patrick Nierlich, B. Döme

Research output: Article

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Abstract

Purpose: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). Experimental Design: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. Results: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P <0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P <0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P <0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P <0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. Conclusions: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.

Original languageEnglish
Pages (from-to)1741-1746
Number of pages6
JournalClinical Cancer Research
Volume15
Issue number5
DOIs
Publication statusPublished - márc. 1 2009

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Vascular Endothelial Growth Factor Receptor-3
Small Cell Lung Carcinoma
Vascular Endothelial Growth Factor C
Endothelial Cells
Neoplasms
Cell Count
Lymph Nodes
Survival
Lymph
Endothelial Progenitor Cells
Bone Marrow Cells
Flow Cytometry
Research Design
Bone Marrow
Enzyme-Linked Immunosorbent Assay
Neoplasm Metastasis
Antibodies
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer. / Bogos, Krisztina; Renyi-Vamos, Ferenc; Dobos, J.; Kenessey, I.; Tóvári, J.; Tímár, J.; Strausz, J.; Ostoros, G.; Klepetko, Walter; Ankersmit, Hendrik Jan; Lang, Gyorgy; Hoda, Mir Alireza; Nierlich, Patrick; Döme, B.

In: Clinical Cancer Research, Vol. 15, No. 5, 01.03.2009, p. 1741-1746.

Research output: Article

Bogos, Krisztina ; Renyi-Vamos, Ferenc ; Dobos, J. ; Kenessey, I. ; Tóvári, J. ; Tímár, J. ; Strausz, J. ; Ostoros, G. ; Klepetko, Walter ; Ankersmit, Hendrik Jan ; Lang, Gyorgy ; Hoda, Mir Alireza ; Nierlich, Patrick ; Döme, B. / High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 5. pp. 1741-1746.
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abstract = "Purpose: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). Experimental Design: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. Results: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P <0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P <0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P <0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P <0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. Conclusions: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.",
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T1 - High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer

AU - Bogos, Krisztina

AU - Renyi-Vamos, Ferenc

AU - Dobos, J.

AU - Kenessey, I.

AU - Tóvári, J.

AU - Tímár, J.

AU - Strausz, J.

AU - Ostoros, G.

AU - Klepetko, Walter

AU - Ankersmit, Hendrik Jan

AU - Lang, Gyorgy

AU - Hoda, Mir Alireza

AU - Nierlich, Patrick

AU - Döme, B.

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Purpose: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). Experimental Design: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. Results: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P <0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P <0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P <0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P <0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. Conclusions: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.

AB - Purpose: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). Experimental Design: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. Results: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P <0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P <0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P <0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P <0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. Conclusions: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.

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U2 - 10.1158/1078-0432.CCR-08-1372

DO - 10.1158/1078-0432.CCR-08-1372

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JO - Clinical Cancer Research

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