• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3045-3050
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• 2014

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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1191-1196
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• 2015

Background: Epidermal growth factor-like domain multiple 7 (EGFL7), recently identified as a secreted protein regulated by oxygen exposure, plays a critical role in promoting metastasis of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) is widely used for treatment of HCC, resulting in hypoxia in tumors and surrounding liver tissues. Accordingly, we proposed the hypothesis that there could be a relationship between expression of EGFL7 and response to TAE. Materials and Methods: We established a rabbit VX2 liver tumor model using percutaneous puncture technique guided by computed tomography. TAE and sham embolization were performed and the results were confirmed by MRI 3 weeks after inoculation. We investigated the EGFL7 expression of the two groups at 6h and 3 days after intervention by means of immunohistochemistry and Western blotting. Results: Immunohistochemical staining demonstrated that the levels of EGFL7 protein significantly increased in the TAE-treated tumors compared with the control group at 6 hours (P=0.031) and 3 days (P=0.020) after intervention. Meanwhile, the relative EGFL7 protein detected in TAE group also up-regulated compared with the control group at 6 hours (P=0.020) and 3 days (P=0.024) after intervention. Conclusions: This study reveals an increase of EGFL7 expression in rabbit VX2 liver tumors after TAE. The role of EGFL7 in HCC, especially its biological behavior after TAE, needs further investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4065-4069
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• 2015

Background: Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. Materials and Methods: EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NCPANC-1, and si-PANC-1 cells, respectively. Results: After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. Conclusions: Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.