title: Targeting EGFL7 expression through RNA interference suppresses renal cell carcinoma growth by inhibiting angiogenesis.
abstract: Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.
authors.affiliation: Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China E-mail : wubin_1959@163.com.
authors.forename: Han-Feng
authors.initials: HF
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Xian-Dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Zhan
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002135:Calcium-Binding Proteins; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000077156:Gefitinib