title: Epidermal growth factor-like domain 7 promotes cell invasion and angiogenesis in pancreatic carcinoma.
abstract: Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, was firstly identified as a modulator of smooth muscle cell migration. Though the expression of EGFL7 was reported to be up-regulated during tumorigenesis, the clinical and biological functions of EGFL7 in pancreatic carcinoma (PC) were still not fully elucidated. In this study, we found that the serum EGFL7 level in PC tissues was statistically higher than that in normal subjects (p<0.001), and its level in non-resectable patients was also higher than that in resectable ones (p=0.013). Among these resectable PC patients, the postoperative EGFL7 expression was significantly down-regulated when tumors were resected (p=0.018). Using the immunohistochemistry method, our results demonstrated that the positive expression of EGFL7 was significantly associated with the TNM stage (p=0.024), lymph node metastasis (p=0.003) and local invasion (p=0.022), and the EGFL7 expression closely correlated to the micro-vessel density (MVD) in PC tissues by Spearman analysis (r=0.941, p=0.000). In vitro, EGFL7 was silenced by the small interference RNA in PC cells, and our data indicated that down-regulation of EGFL7 did not influence the cycle progression, proliferation, colony formation and apoptosis of PC cells (p>0.05), whereas inhibition of EGFL7 expression could decrease PaCa-2 cell invasion (p<0.05). More interestingly, by tubular formation, Chick embryo chorioallantoic membrane (CAM) and ELISA assays, our results revealed that silencing EGFL7 expression represented a strong inhibiting effect on tubular formation of micro-vessels through down-regulating the protein levels of VEGF and Ang-2 (p<0.05). Our results raised the possibility of using EGFL7as a potential prognostic biomarker and therapy target of PC, and down-regulation of EGFL7 might be considered to be a potentially important molecular treatment strategy for patients with PC.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Guo
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Dechun
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: 13913506369@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: strexboy@163.com.
authors.forename: Qiaoming
authors.initials: Q
authors.lastname: Zhi
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; D034741:RNA, Small Interfering
keywords: Angiogenesis; EGFL7; Invasion; Pancreatic carcinoma