Targeting EGFL7 Expression through RNA Interference Suppresses Renal Cell Carcinoma Growth by Inhibiting Angiogenesis

Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely relatedwith its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domainmultiple 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 isnot clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture systemin vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migrationand tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesionkinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells wassignificantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylationwas abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group wasnoticeably 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.