Endothelial cell colony forming units derived from malignant breast diseases are resistant to tumor necrosis factor-α-induced apoptosis

• Published in: Scientific reports 2016-11, Vol.6 (1), p.37450-37450, Article 37450
• Main Authors: Chou, Chen-Pin, Jiang, Shih Sheng, Pan, Huay-Ben, Yen, Yi-Chen, Tseng, Hui-Hwa, Hung, Yu-Ting, Wang, Ssu-Han, Chen, Yu-Lin, Chen, Ya-Wen
• Format: Article
• Language: English
• Subjects: 45/100; 49/39; 631/67/71; 692/4017; Adult; Antigens, CD34 - genetics; Antigens, CD34 - metabolism; Apoptosis - drug effects; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Intraductal, Noninfiltrating - diagnosis; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - pathology; Carcinoma, Lobular - diagnosis; Carcinoma, Lobular - genetics; Carcinoma, Lobular - metabolism; Carcinoma, Lobular - pathology; Carcinoma, Papillary - diagnosis; Carcinoma, Papillary - genetics; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; Case-Control Studies; Colony-Forming Units Assay; Diagnosis, Differential; Disease Resistance - genetics; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Endothelial Progenitor Cells - pathology; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Hyperplasia - diagnosis; Hyperplasia - genetics; Hyperplasia - metabolism; Hyperplasia - pathology; Middle Aged; multidisciplinary; Primary Cell Culture; Receptors, Tumor Necrosis Factor, Type II - genetics; Receptors, Tumor Necrosis Factor, Type II - metabolism; Science; Signal Transduction; Stem Cells - metabolism; Stem Cells - pathology; Tumor Necrosis Factor-alpha - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep37450

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.