Distinctive properties of endothelial cells from tumor and normal tissue in human breast cancer

Tumor microenvironment shapes aggressiveness and is largely maintained by the conditions of angiogenesis formation. Thus endothelial cells (ECs) biological reactions are crucial to know and control the design of efficient therapies. Here we used a model of ECs representative for the breast cancer tumor site and the same but healthy organ. Cells characterization was performed at the transcriptome, protein expression levels and assessment of their functional biological responses: angiogenesis and permeability. We showed that the expression of proteins specific for ECs (ACE+, VWF+), their differentiation (CD31+, CD 133+, CD105+, CD34-), adhesion properties (ICAM-1+, VCAM-1+, CD62-L+), barrier formation (ZO-1+) were down-regulated in tumor-derived ECs. The NGS-based differential transcriptome analysis confirmed CD31-lowered expression and pointed to the increase of Ephrin-B2 and SNCAIP indicative for dedifferentiation. Functional assays confirmed these differences as angiogenesis was impaired while permeability increased in tumor-derived ECs, further validated by the distinct enhanced VEGF production in response to hypoxia, reflecting the tumor conditions. This work shows that endothelial cells differ highly significantly, both phenotypically and functionally in the tumor site vs. the normal corresponding tissue, influencing the tumor microenvironment. Overall design: RNA-Seq for normal cells (2 replicates) and breast cancer cells (2 replicates)