title: Genome-wide analysis of the effect of esophageal squamous cell carcinoma on human umbilical vein endothelial cells.
abstract: A large volume of data indicates that controlling tumor-associated angiogenesis is a promising therapy against cancer. However, angiogenesis is a complex process, little is known about the differential gene expression in the process of normal endothelial cell differentiation toward tumor vascular endothelial cells induced by tumor microenvironment. The aim of this study is to investigate the effect of tumor microenvironment simulated by the supernatant of esophageal squamous cancer cells (KYSE70) on normal endothelial cells (HUVECs) at the whole genome level. The gene expression profile was studied through gene ontology and signal pathway analysis. Compared with the normal HUVECs, a total of 3769 differentially expressed genes in induced HUVECs were detected, including 1609 upregulated genes and 2160 downregulated genes. Moreover, the microarray data analysis showed that 11 significant biological processes and 10 significant signaling pathways changed most, which are associated with angiogenesis and cell differentiation. According to the different expression levels in the microarrays and their functions, four differentially expressed genes involved in tumor angiogenesis and cell differentiation (IL6, VEGFA, S1PR1, TYMP) were selected and analyzed by qRT-PCR. The qRT-PCR results were consistent with the microarray data. Furthermore, we simulated the tumor microenvironment by human esophageal carcinoma tissue homogenate to investigate its effect on HUVECs, the qRT-PCR results indicated that the above genes were highly expressed in HUVECs after induction by esophageal carcinoma tissue homogenate. In conclusion, tumor microenvironment impact on normal endothelial cells differentiated toward tumor vascular endothelial cells, and the selected genes, which are associated with tumor angiogenesis, would be anti-angiogenesis targets against esophageal carcinoma.
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Guoguo
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Hangfan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Kangdong
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Xinhuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D005819:Genetic Markers; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase