LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

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.

Important!

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

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Krajewska, E.; Lewis, C.E.; Chen, Y.Y.; Welford, A.; Tazzyman, S.; Staton, C.A. (2010)
Publisher: Cancer Research UK
Languages: English
Types: Article
Subjects:
Background: Angiogenesis and haemostasis are closely linked within tumours with many haemostatic proteins regulating tumour angiogenesis. Indeed we previously identified a fragment of human fibrinogen, fibrinogen E-fragment (FgnE) with potent anti-angiogenic properties in vitro and cytotoxic effects on tumour vessels in vivo. We therefore investigated which region of FgnE was mediating vessel cytotoxicity.\ud \ud Methods: Human dermal microvascular endothelial cells (ECs) were used to test the efficacy of peptides derived from FgnE on proliferation, migration, differentiation, apoptosis and adhesion before testing the efficacy of an active peptide on tumour vasculature in vivo.\ud \ud Results: We identified a 20-amino-acid peptide derived from the β chain of FgnE, β43–63, which had no effect on EC proliferation or migration but markedly inhibited the ability of activated ECs to form tubules or to adhere to various constituents of the extracellular matrix – collagen IV, fibronectin and vitronectin. Furthermore, our data show that β43–63 interacts with ECs, in part, by binding to αvβ3, so soluble αvβ3 abrogated β43–63 inhibition of tubule formation by activated ECs. Finally, when injected into mice bearing tumour xenografts, β43–63 inhibited tumour vascularisation and induced formation of significant tumour necrosis.\ud \ud Conclusions: Taken together, these data suggest that β43–63 is a novel anti-tumour peptide whose anti-angiogenic effects are mediated by αvβ3.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Beckstead J (1994) A simple technique for preservation of fixation sensitive antigens in paraffin-embedded tissues. J Histochem Cytochem 42: 1127 - 1134
    • Bootle-Wilbraham CA, Tazzyman S, Marshall JM, Lewis CE (2000) Fibrinogen E-fragment inhibits the migration and tubule formation of human dermal microvascular endothelial cells in vitro. Cancer Res 60: 4719 - 4724
    • Borges E, Jan Y, Ruoslahti E (2000) Platelet derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain. J Biol Chem 275: 39867 - 39873
    • Brown NJ, Staton CA, Rodgers GR, Corke KP, Underwood JCE, Lewis CE (2002) Fibrinogen E-fragment selectively disrupts the vasculature and inhibits the growth of tumors in a synergic murine model. Br J Cancer 86: 1813 - 1816
    • Chua CC, Rahimi N, Forsten-Williams K, Nugent MA (2004) Heparan sulfate proteoglycans function as receptors for fibroblast growth factor-2 activation of extracellular signal-regulated kinases 1 and 2. Circ Res 94: 316 - 323
    • Collingridge HAS, Chaplin DJ (2001) Proportion of infiltrating IgG binding immune cells predict for tumour hypoxia. Br J Cancer 84: 626 - 630
    • Daly ME, Makris A, Reed M, Lewis CE (2003) Hemostatic regulators of tumor angiogenesis: a source of antiangiogenic agents for cancer treatment? J Natl Cancer Inst 95: 660 - 673
    • Delaney CE, Weagant BT, Addison CL (2006) The inhibitory effects of endostatin on endothelial cells are modulated by extracellular matrix. Exp Cell Res 312: 2476 - 2489
    • Doolittle R (1981) Fibrinogen and fibrin. Sci Am 245: 92 - 101
    • Eliceiri BP (2001) Integrin and growth factor receptor crosstalk. Circ Res 89: 1104 - 1110
    • Ellis IR, Schor AM, Schor SL (2007) EGF and TGF-alpha motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms. Exp Cell Res 313: 732 - 741
    • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nat Med 1: 27 - 31
    • Hynes RO (2007) Cell-matrix adhesion in vascular development. J Thromb Haemost 5: 32 - 40
    • Kemp LE, Mulloy B, Gherardi E (2006) Signalling by HGF/SF and Met: the role of heparin sulphate co-receptors. Biochem Soc Trans 34: 414 - 417
    • Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR (1986) Basement membrane complexes with biological activity. Biochemistry 25: 312 - 318
    • Kucharzewska P, Welch JE, Svensson KJ, Belting M (2009) The polyamines regulate endothelial cell survival during hypoxic stress through PI3K/ AKT and MCL-1. Biochem Biophys Res Commun 380: 413 - 418
    • Maeshima Y, Colorado PC, Kalluri R (2000) Two RGD-independent alpha v beta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. J Biol Chem 275: 23745 - 23750
    • Maeshima Y, Sudhakar A, Lively JC, Ueki K, Kharbanda S, Kahn CR, Sonenberg N, Hynes RO, Kalluri R (2002) Tumstatin, an endothelial cellspecific inhibitor of protein synthesis. Science 295: 140 - 143
    • Maeshima Y, Yerramalla UL, Dhanabal M, Holthaus KA, Barbashov S, Kharbanda S, Reimer C, Manfredi M, Dickerson WM, Kalluri R (2001) Extracellular matrix-derived peptide binds to alpha(v)beta(3) integrin and inhibits angiogenesis. J Biol Chem 276: 31959 - 31968
    • Malinda KM, Ponce L, Kleinman HK, Shackelton LM, Millis AJ (1999) Gp38k, a protein synthesized by vascular smooth muscle cells. Exp Cell Res 250: 168 - 173
    • Mizejewski GJ (1999) Role of integrins in cancer: survey of expression patterns. Proc Soc Exp Biol Med 222: 124 - 138
    • Mundel TM, Kalluri R (2007) Type IV collagen-derived angiogenesis inhibitors. Microvasc Res 74: 85 - 89
    • Neufeld G, Tessler S, Gitay-Goren H, Cohen T, Levi BZ (1994) Vascular endothelial growth factor and its receptors. Prog Growth Factor Res 5: 89 - 97
    • Park K, Kim YS, Lee GY, Park RW, Kim IS, Byun Y (2008) Tumour endothelial targeted cyclic RGD-modified heparin derivative: inhibition of angiogenesis and tumour growth. Pharm Res 25: 2786 - 2798
    • Ru¨egg C, Mariotti A (2003) Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis. Cell Mol Life Sci 60: 1135 - 1157
    • Sahni A, Francis CW (2004) Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires alphavbeta3. Blood 104: 3635 - 3641
    • Saito Y, Shiota Y, Nishisaka M, Owaki T, Shimamura M, Fukai F (2008) Inhibition of angiogenesis by a tenascin-c peptide which is capable of activating beta1-integrins. Biol Pharm Bull 31: 1003 - 1007
    • Soldi R, Mitola S, Strasly M, Defilippi P, Tarone G, Bussolino F (1999) Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor 2. EMBO J 18: 882 - 892
    • Staton CA, Brown NJ, Rodgers GR, Corke KP, Tazzyman S, Underwood JC, Lewis CE (2004) Alphastatin, a 24-amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo. Blood 103: 601 - 606
    • Yakovlev S, Gorlatov S, Ingham K, Medved L (2003) Interaction of fibrin(ogen) with heparin: further characterization and localization of the heparin binding site. Biochemistry 42: 709 - 716
    • Yokoyama K, Zhang XP, Medved L, Takada Y (1999) Specific binding of integrin alpha v beta 3 to the fibrinogen gamma and alpha E chain Cterminal domains. Biochemistry 38: 5872 - 5877
    • Zacharski LR, Memoli VA, Rousseau SM (1986) Coagulation-cancer interaction in situ in renal cell carcinoma. Blood 68: 394 - 399
  • No related research data.
  • Discovered through pilot similarity algorithms. Send us your feedback.

Share - Bookmark

Cite this article