Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Sanders, Andrew James; Ye, Lin; Li, Jin; Mason, Malcolm David; Jiang, Wen Guo (2014)
Publisher: Spandidos Publications
Languages: English
Types: Article
Subjects: RC0254
Hepatocyte growth factor (HGF) is a key growth factor linked to promoting cancer progression and angiogenesis. The present study identifies repulsive guidance molecule b (RGMb), a bone morphogenetic protein (BMP) co-receptor, as a gene whose expression is regulated by HGF and explores the potential of RGMb to contribute to the process of angiogenesis. Microarray analysis was used to identify HGF responsive genes in HECV endothelial cells, identifying RGMb. RGMb was subsequently targeted using a ribozyme transgene system and its role in angiogenesis assessed using in vitro and in vivo assays. The importance of RGMb in pro-angiogenic responses to HGF and BMP-7 was also assessed. Microarray analysis identified RGMb as a gene upregulated as a result of HGF treatment. Knockdown of RGMb, in HECV cells, had minimal effects on tubule formation, brought about a general, although non-significant increase in cell growth and enhanced cell migration. Similarly, no significant effect of RGMb knockdown was found in vivo using a co-inoculation angiogenesis model. Knockdown of RGMb was, however, found to reduce the responsiveness of HECV cells to HGF treatment and particularly to BMP-7 treatment in regard to the enhanced migratory and tubule formation brought about by these treatments in vitro. Our results indicate that RGMb expression can be influenced by HGF treatment. Whilst this molecule appears to have minimal impact on angiogenic traits individually, it demonstrates an involvement in propagating pro-angiogenic effects of HGF and particularly BMP-7 and thus, may play a role in regulating angiogenic responses to HGF and BMP-7.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Folkman J: Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6: 273-286, 2007.
    • 2. Potente M, Gerhardt H and Carmeliet P: Basic and therapeutic aspects of angiogenesis. Cell 146: 873-887, 2011.
    • 3. Jiang WG, Martin TA, Parr C, Davies G, Matsumoto K and Nakamura T: Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. Crit Rev Oncol Hematol 53: 35-69, 2005.
    • 4. Wojta J, Kaun C, Breuss JM, et al: Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Lab Invest 79: 427-438, 1999.
    • 5. Davies G, Mason MD, Martin TA, et al: The HGF/SF antagonist NK4 reverses bfiroblast- and HGF-induced prostate tumor growth and angiogenesis in vivo. Int J Cancer 106: 348-354, 2003.
    • 6. Martin TA, Parr C, Davies G, et al: Growth and angiogenesis of human breast cancer in a nude mouse tumour model is reduced by NK4, a HGF/SF antagonist. Carcinogenesis 24: 1317-1323, 2003.
    • 7. Monnier PP, Sierra A, Macchi P, et al: RGM is a repulsive guidance molecule for retinal axons. Nature 419: 392-395, 2002.
    • 8. Oldekamp J, Kramer N, Alvarez-Bolado G and Skutella T: Expression pattern of the repulsive guidance molecules RGM A, B and C during mouse development. Gene Expr Patterns 4: 283-288, 2004.
    • 9. Schmidtmer J and Engelkamp D: Isolation and expression pattern of three mouse homologues of chick Rgm. Gene Expr Patterns 4: 105-110, 2004.
    • 10. Niederkofler V, Salie R, Sigrist M and Arber S: Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J Neurosci 24: 808-818, 2004.
    • 11. Samad TA, Srinivasan A, Karchewski LA, et al: DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neurosci 24: 2027-2036, 2004.
    • 12. Ma CH, Brenner GJ, Omura T, et al: The BMP coreceptor RGMb promotes while the endogenous BMP antagonist noggin reduces neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling. J Neurosci 31: 18391-18400, 2011.
    • 13. Liu X, Hashimoto M, Horii H, Yamaguchi A, Naito K and Yamashita T: Repulsive guidance molecule b inhibits neurite growth and is increased after spinal cord injury. Biochem Biophys Res Commun 382: 795-800, 2009.
    • 14. Samad TA, Rebbapragada A, Bell E, et al: DRAGON, a bone morphogenetic protein co-receptor. J Biol Chem 280: 14122-14129, 2005.
    • 15. Babitt JL, Zhang Y, Samad TA, et al: Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morpho - genetic protein co-receptor. J Biol Chem 280: 29820-29827, 2005.
    • 16. Babitt JL, Huang FW, Wrighting DM, et al: Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38: 531-539, 2006.
    • 17. Halbrooks PJ, Ding R, Wozney JM and Bain G: Role of RGM coreceptors in bone morphogenetic protein signaling. J Mol Signal 2: 4, 2007.
    • 18. Xia Y, Sidis Y, Mukherjee A, et al: Localization and action of Dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis. Endocrinology 146: 3614-3621, 2005.
    • 19. Xia Y, Cortez-Retamozo V, Niederkofler V, et al: Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages. J Immunol 186: 1369-1376, 2011.
    • 20. Li J, Ye L, Mansel RE and Jiang WG: Potential prognostic value of repulsive guidance molecules in breast cancer. Anticancer Res 31: 1703-1711, 2011.
    • 21. Li J, Ye L, Kynaston HG and Jiang WG: Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells. Int J Oncol 40: 544-550, 2012.
    • 22. Li J, Ye L, Sanders AJ and Jiang WG: Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling. J Cell Biochem 113: 2523-2531, 2012.
    • 23. Sanders AJ, Parr C, Mason MD and Jiang WG: Suppression of hepatocyte growth factor activator inhibitor-1 leads to a more aggressive phenotype of prostate cancer cells in vitro. Int J Mol Med 20: 613-619, 2007.
    • 24. Yuan Z, Sanders AJ, Ye L, Wang Y and Jiang WG: Knockdown of human antigen R reduces the growth and invasion of breast cancer cells in vitro and affects expression of cyclin D1 and MMP-9. Oncol Rep 26: 237-245, 2011.
    • 25. Zuker M: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31: 3406-3415, 2003.
    • 26. Parr C, Sanders AJ, Davies G, et al: Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patients. Clin Cancer Res 13: 3568-3576, 2007.
    • 27. Parr C, Watkins G, Mansel RE and Jiang WG: The hepatocyte growth factor regulatory factors in human breast cancer. Clin Cancer Res 10: 202-211, 2004.
    • 28. Jiang WG, Hiscox SE, Parr C, et al: Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Clin Cancer Res 5: 3695-3703, 1999.
    • 29. Sanders AJ, Ye L, Mason MD and Jiang WG: The impact of EPLINalpha (Epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis. Angiogenesis 13: 317-326, 2010.
    • 30. David L, Feige JJ and Bailly S: Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 20: 203-212, 2009.
    • 31. Cai J, Pardali E, Sanchez-Duffhues G and ten Dijke P: BMP signaling in vascular diseases. FEBS Lett 586: 1993-2002, 2012.
    • 32. Ye L, Lewis-Russell JM, Davies G, Sanders AJ, Kynaston H and Jiang WG: Hepatocyte growth factor up-regulates the expression of the bone morphogenetic protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells. Int J Oncol 30: 521-529, 2007.
    • 33. Ye L, Lewis-Russell JM, Sanders AJ, Kynaston H and Jiang WG: HGF/SF up-regulates the expression of bone morphogenetic protein 7 in prostate cancer cells. Urol Oncol 26: 190-197, 2008.
    • 34. Kanomata K, Kokabu S, Nojima J, Fukuda T and Katagiri T: DRAGON, a GPI-anchored membrane protein, inhibits BMP signaling in C2C12 myoblasts. Genes Cells 14: 695-702, 2009.
  • No related research data.
  • Discovered through pilot similarity algorithms. Send us your feedback.

Share - Bookmark

Cite this article