High VEGFR-3–positive Circulating Lymphatic/Vascular Endothelial Progenitor Cell Level Is Associated with Poor Prognosis in Human Small Cell Lung Cancer

• Published in: Clinical cancer research 2009-03, Vol.15 (5), p.1741-1746
• Main Authors: BOGOS, Krisztina, RENYI-VAMOS, Ferenc, LANG, Gyorgy, ALIREZA HODA, Mir, NIERLICH, Patrick, DOME, Balazs, DOBOS, Judit, KENESSEY, Istvan, TOVARI, Jozsef, TIMAR, Jozsef, STRAUSZ, Janos, OSTOROS, Gyula, KLEPETKO, Walter, ANKERSMIT, Hendrikjan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Bone Marrow - metabolism; Bone Marrow - pathology; Case-Control Studies; Disease Progression; Endothelial Cells - metabolism; Endothelial Cells - pathology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Follow-Up Studies; Humans; Lung - metabolism; Lung - pathology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; lymph node metastasis; Lymphatic Metastasis; Lymphatic Vessels - metabolism; Lymphatic Vessels - pathology; lymphatic/vascular endothelial progenitor cells; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pneumology; Prognosis; small cell lung cancer; Small Cell Lung Carcinoma - metabolism; Small Cell Lung Carcinoma - pathology; Stem Cells - metabolism; Stem Cells - pathology; Survival Rate; Tumors of the respiratory system and mediastinum; Vascular Endothelial Growth Factor C - blood; Vascular Endothelial Growth Factor Receptor-3 - blood; vascular endothelial growth factor-C
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-1372

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.