Abstract
Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34+ VEGFR2+ EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antigens, CD34 / genetics
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Antigens, CD34 / metabolism
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Apoptosis / drug effects
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Breast Neoplasms / diagnosis*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Carcinoma, Intraductal, Noninfiltrating / diagnosis*
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Carcinoma, Intraductal, Noninfiltrating / genetics
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Carcinoma, Intraductal, Noninfiltrating / metabolism
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Carcinoma, Intraductal, Noninfiltrating / pathology
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Carcinoma, Lobular / diagnosis*
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Carcinoma, Lobular / genetics
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Carcinoma, Lobular / metabolism
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Carcinoma, Lobular / pathology
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Carcinoma, Papillary / diagnosis*
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Carcinoma, Papillary / genetics
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Carcinoma, Papillary / metabolism
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Carcinoma, Papillary / pathology
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Case-Control Studies
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Colony-Forming Units Assay
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Diagnosis, Differential
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Disease Resistance / genetics
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Endothelial Progenitor Cells / drug effects
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Endothelial Progenitor Cells / metabolism*
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Endothelial Progenitor Cells / pathology
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Female
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic*
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Humans
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Hyperplasia / diagnosis*
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Hyperplasia / genetics
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Hyperplasia / metabolism
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Hyperplasia / pathology
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Middle Aged
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Primary Cell Culture
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Receptors, Tumor Necrosis Factor, Type II / genetics
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Receptors, Tumor Necrosis Factor, Type II / metabolism
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Signal Transduction
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Stem Cells / metabolism
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Stem Cells / pathology
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Tumor Necrosis Factor-alpha / pharmacology
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Antigens, CD34
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor-alpha
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KDR protein, human
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Vascular Endothelial Growth Factor Receptor-2