Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Xu, Han-Feng (Department of Urology, Shengjing Hospital of China Medical University) ;
  • Chen, Lei (Department of Surgery, Hunan Polytechnic of Environment and Biology) ;
  • Liu, Xian-Dong (Department of Urology, Shengjing Hospital of China Medical University) ;
  • Zhan, Yun-Hong (Department of Urology, Shengjing Hospital of China Medical University) ;
  • Zhang, Hui-Hui (Department of Urology, First Affiliated Hospital of Nanhua University) ;
  • Li, Qing (Department of Urology, First Affiliated Hospital of Nanhua University) ;
  • Wu, Bin (Department of Urology, Shengjing Hospital of China Medical University)
  • Published : 2014.04.01
Download PDF
⟨ Previous Next ⟩

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.

Keywords

References

  1. Cairns P (2010). Renal cell carcinoma. Cancer Biomark, 9, 461-73.
  2. Campagnolo L, Leahy A, Chitnis S, et al (2005). EGFL7 is a chemoattractant for endothelial cells and is up-regulated in angiogenesis and arterial injury. Am J Pathol, 167, 275-84. https://doi.org/10.1016/S0002-9440(10)62972-0
  3. Carmeliet P, Jain RK (2000). Angiogenesis in cancer and other diseases. Nature, 407, 249-57. https://doi.org/10.1038/35025220
  4. Carmeliet P, Jain RK (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature, 473, 298-307. https://doi.org/10.1038/nature10144
  5. Chung AS, Lee J, Ferrara N (2010). Targeting the tumour vasculature: insights from physiological angiogenesis. Nat Rev Cancer, 10, 505-14. https://doi.org/10.1038/nrc2868
  6. Cohen HT, McGovern FJ (2005). Renal-cell carcinoma. N Engl J Med, 353, 2477-90. https://doi.org/10.1056/NEJMra043172
  7. Diaz R, Silva J, Garcia JM, et al (2008). Deregulated expression of miR-106a predicts survival in human colon cancer patients. Genes Chromosomes Cancer, 47, 794-802. https://doi.org/10.1002/gcc.20580
  8. Fitch MJ, Campagnolo L, Kuhnert F, Stuhlmannh (2004). Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial cells. Dev Dyn, 230, 316-24. https://doi.org/10.1002/dvdy.20063
  9. Folkman J (2002). Role of angiogenesis in tumor growth and metastasis. Semin Oncol, 29, 15-8. https://doi.org/10.1053/sonc.2002.37263
  10. Grunwald V, Ravaud A (2014). Systemic therapy of renal cell carcinoma. World J Urol, 32, 1. https://doi.org/10.1007/s00345-013-1226-9
  11. Huang CH, Li XJ, Zhou YZ, et al (2010). Expression and clinical significance of EGFL7 in malignant glioma. J Cancer Res Clin Oncol, 136, 1737-43. https://doi.org/10.1007/s00432-010-0832-9
  12. Nikolic I, Stankovic ND, Bicker F, et al (2013). EGFL7 ligates alphavbeta3 integrin to enhance vessel formation. Blood, 121, 3041-50. https://doi.org/10.1182/blood-2011-11-394882
  13. Parker LH, Schmidt M, Jin SW, et al (2004). The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature, 428, 754-8. https://doi.org/10.1038/nature02416
  14. Rini BI, Campbell SC, Escudier B (2009). Renal cell carcinoma. Lancet, 373, 1119-32. https://doi.org/10.1016/S0140-6736(09)60229-4
  15. Schmidt M, Paes K, De Maziere A, et al (2007). EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development, 134, 2913-23. https://doi.org/10.1242/dev.002576
  16. Shojaei F (2012). Anti-angiogenesis therapy in cancer: current challenges and future perspectives. Cancer Lett, 320, 130-7. https://doi.org/10.1016/j.canlet.2012.03.008
  17. Sieg DJ, Hauck CR, Ilic D, et al (2000). FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol, 2, 249-56. https://doi.org/10.1038/35010517
  18. Sun Y, Bai Y, Zhang F, et al (2010). miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7. Biochem Biophys Res Commun, 391, 1483-9. https://doi.org/10.1016/j.bbrc.2009.12.098
  19. Tanriverdi O (2013). Review on targeted treatment of patients with advanced-stage renal cell carcinoma: a medical oncologist's perspective. Asian Pac J Cancer Prev, 14, 609-17. https://doi.org/10.7314/APJCP.2013.14.2.609
  20. Weis SM, Cheresh DA (2011). Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med, 17, 1359-70. https://doi.org/10.1038/nm.2537
  21. Wu F, Yang LY, Li YF, et al (2009). Novel role for epidermal growth factor-like domain 7 in metastasis of human hepatocellular carcinoma. Hepatology, 50, 1839-50. https://doi.org/10.1002/hep.23197

Cited by

  1. Drug Resistance Effects of Ribosomal Protein L24 Overexpression in Hepatocellular Carcinoma HepG2 Cells vol.15, pp.22, 2014, https://doi.org/10.7314/APJCP.2014.15.22.9853
  2. Expression of Epidermal Growth Factor-like Domain 7 is Increased by Transcatheter Arterial Embolization of Liver Tumors vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.1191
  3. Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.4065
  4. Inhibits Angiogenesis and Growth of Renal Cell Carcinoma in a Nude Mouse Xenograft Model vol.34, pp.12, 2015, https://doi.org/10.1089/dna.2015.2918
  5. EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/β-catenin signaling vol.119, pp.12, 2018, https://doi.org/10.1002/jcb.27375
  6. EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis vol.233, pp.11, 2018, https://doi.org/10.1002/jcp.26792