Skip to main content

Advertisement

SpringerLink
Log in

The roles of ADAMTS in angiogenesis and cancer

  • Review
  • Published:
Tumor Biology

Abstract

Angiogenesis is an indispensable mechanism involved in both physiological processes and various pathological conditions, such as inflammation, aberrant wound healing, tumor progression, and metastasis. Among many angiogenic stimulators and inhibitors, vascular endothelial growth factor (VEGF) is regarded as one of the most important members of the signaling protein family involved in blood vessel formation and maturation. The a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) proteins are a family of multifunctional proteinases. Such proteolytic enzymes are associated with various physiological processes, such as collagen maturation, organogenesis, angiogenesis, and reproduction. Importantly, deficiency or overexpression of certain ADAMTS proteinases has been shown to be directly involved in a number of serious diseases, including tumor progression and metastasis. This review explores in-depth the connections between ADAMTS proteinases as positive/negative mediators during angiogenesis and VEGF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kuno K, Kanada N, Nakashima E, Fujiki F, Ichimura F, Matsushima K. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem. 1997;272(1):556–62.

    CAS  PubMed  Google Scholar 

  2. Folkman J. Angiogenesis. Annu Rev Med. 2006;57:1–18.

    CAS  PubMed  Google Scholar 

  3. Ferrara N. VEGF as a therapeutic target in cancer. Oncology. 2005;69 Suppl 3:11–6.

    CAS  PubMed  Google Scholar 

  4. Yoo SY, Kwon SM. Angiogenesis and its therapeutic opportunities. Mediat Inflamm. 2013;2013:127170.

    Google Scholar 

  5. Gimbrone Jr MA, Cotran RS, Leapman SB, Folkman J. Tumor growth and neovascularization: an experimental model using the rabbit cornea. J Natl Cancer Inst. 1974;52(2):413–27.

    PubMed  Google Scholar 

  6. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182–6.

    CAS  PubMed  Google Scholar 

  7. Samples J, Willis M, Klauber-Demore N. Targeting angiogenesis and the tumor microenvironment. Surg Oncol Clin N Am. 2013;22(4):629–39.

    PubMed  PubMed Central  Google Scholar 

  8. Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr Top Microbiol Immunol. 1999;237:97–132.

    CAS  PubMed  Google Scholar 

  9. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146(5):1029–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Shibuya M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct. 2001;26(1):25–35.

    CAS  PubMed  Google Scholar 

  11. Okada F, Rak JW, Croix BS, Lieubeau B, Kaya M, Roncari L, et al. Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc Natl Acad Sci U S A. 1998;95(7):3609–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Iliopoulos O, Levy AP, Jiang C, Kaelin Jr WG, Goldberg MA. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci U S A. 1996;93(20):10595–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kampen KR. The mechanisms that regulate the localization and overexpression of VEGF receptor-2 are promising therapeutic targets in cancer biology. Anticancer Drugs. 2012;23(4):347–54.

    CAS  PubMed  Google Scholar 

  14. Brown LF, Berse B, Jackman RW, Tognazzi K, Guidi AJ, Dvorak HF, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol. 1995;26(1):86–91.

    CAS  PubMed  Google Scholar 

  15. Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS metalloproteinases. Biochem J. 2005;386(Pt 1):15–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Hurskainen TL, Hirohata S, Seldin MF, Apte SS. ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family. J Biol Chem. 1999;274(36):25555–63.

    CAS  PubMed  Google Scholar 

  17. Luque A, Carpizo DR, Iruela-Arispe ML. ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165. J Biol Chem. 2003;278(26):23656–65.

    CAS  PubMed  Google Scholar 

  18. Apte SS. A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem. 2009;284(46):31493–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Clark ME, Kelner GS, Turbeville LA, Boyer A, Arden KC, Maki RA. ADAMTS9, a novel member of the ADAM-TS/metallospondin gene family. Genomics. 2000;67(3):343–50.

    CAS  PubMed  Google Scholar 

  20. Nardi JB, Martos R, Walden KK, Lampe DJ, Robertson HM. Expression of lacunin, a large multidomain extracellular matrix protein, accompanies morphogenesis of epithelial monolayers in Manduca sexta. Insect Biochem Mol Biol. 1999;29(10):883–97.

    CAS  PubMed  Google Scholar 

  21. Jones GC, Riley GP. ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis. Arthritis Res Ther. 2005;7(4):160–9.

    PubMed  PubMed Central  Google Scholar 

  22. Zheng X, Chung D, Takayama TK, Majerus EM, Sadler JE, Fujikawa K. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276(44):41059–63.

    CAS  PubMed  Google Scholar 

  23. Gao G, Westling J, Thompson VP, Howell TD, Gottschall PE, Sandy JD. Activation of the proteolytic activity of ADAMTS4 (aggrecanase-1) by C-terminal truncation. J Biol Chem. 2002;277(13):11034–41.

    CAS  PubMed  Google Scholar 

  24. Kuno K, Matsushima K. ADAMTS-1 protein anchors at the extracellular matrix through the thrombospondin type I motifs and its spacing region. J Biol Chem. 1998;273(22):13912–7.

    CAS  PubMed  Google Scholar 

  25. Rocks N, Paulissen G, El Hour M, Quesada F, Crahay C, Gueders M, et al. Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie. 2008;90(2):369–79.

    CAS  PubMed  Google Scholar 

  26. Stanton H, Melrose J, Little CB, Fosang AJ. Proteoglycan degradation by the ADAMTS family of proteinases. Biochim Biophys Acta. 2011;1812(12):1616–29.

    CAS  PubMed  Google Scholar 

  27. Tang BL. ADAMTS: a novel family of extracellular matrix proteases. Int J Biochem Cell Biol. 2001;33(1):33–44.

    CAS  PubMed  Google Scholar 

  28. Kuno K, Okada Y, Kawashima H, Nakamura H, Miyasaka M, Ohno H, et al. ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan. FEBS Lett. 2000;478(3):241–5.

    CAS  PubMed  Google Scholar 

  29. Rodriguez-Manzaneque JC, Westling J, Thai SN, Luque A, Knauper V, Murphy G, et al. ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitors. Biochem Biophys Res Commun. 2002;293(1):501–8.

    CAS  PubMed  Google Scholar 

  30. Ricciardelli C, Frewin KM, Tan Ide A, Williams ED, Opeskin K, Pritchard MA, et al. The ADAMTS1 protease gene is required for mammary tumor growth and metastasis. Am J Pathol. 2011;179(6):3075–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, et al. ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev Cell. 2009;17(5):687–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Tortorella MD, Malfait AM, Deccico C, Arner E. The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation. Osteoarthr Cartil. 2001;9(6):539–52.

    CAS  PubMed  Google Scholar 

  33. Matthews RT, Gary SC, Zerillo C, Pratta M, Solomon K, Arner EC, et al. Brain-enriched hyaluronan binding (BEHAB)/brevican cleavage in a glioma cell line is mediated by a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family member. J Biol Chem. 2000;275(30):22695–703.

    CAS  PubMed  Google Scholar 

  34. Sandy JD, Westling J, Kenagy RD, Iruela-Arispe ML, Verscharen C, Rodriguez-Mazaneque JC, et al. Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. J Biol Chem. 2001;276(16):13372–8.

    CAS  PubMed  Google Scholar 

  35. Nakamura M, Sone S, Takahashi I, Mizoguchi I, Echigo S, Sasano Y. Expression of versican and ADAMTS1, 4, and 5 during bone development in the rat mandible and hind limb. J Histochem Cytochem. 2005;53(12):1553–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Kuno K, Terashima Y, Matsushima K. ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix. J Biol Chem. 1999;274(26):18821–6.

    CAS  PubMed  Google Scholar 

  37. Somerville RP, Longpre JM, Jungers KA, Engle JM, Ross M, Evanko S, et al. Characterization of ADAMTS-9 and ADAMTS-20 as a distinct ADAMTS subfamily related to Caenorhabditis elegans GON-1. J Biol Chem. 2003;278(11):9503–13.

    CAS  PubMed  Google Scholar 

  38. Collins-Racie LA, Flannery CR, Zeng W, Corcoran C, Annis-Freeman B, Agostino MJ, et al. ADAMTS-8 exhibits aggrecanase activity and is expressed in human articular cartilage. Matrix Biol. 2004;23(4):219–30.

    CAS  PubMed  Google Scholar 

  39. Yamaji NK., Nishimura K., Abe O., Ohara T., Nagase and N. Nomura, Novel metalloprotease having aggrecanase activity. 2004, Google Patents.

  40. Wang WM, Lee S, Steiglitz BM, Scott IC, Lebares CC, Allen ML, et al. Transforming growth factor-beta induces secretion of activated ADAMTS-2. A procollagen III N-proteinase. J Biol Chem. 2003;278(21):19549–57.

    CAS  PubMed  Google Scholar 

  41. Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W, et al. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am J Hum Genet. 1999;65(2):308–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Nusgens BV, Verellen-Dumoulin C, Hermanns-Le T, De Paepe A, Nuytinck L, Pierard GE, et al. Evidence for a relationship between Ehlers-Danlos type VII C in humans and bovine dermatosparaxis. Nat Genet. 1992;1(3):214–7.

    CAS  PubMed  Google Scholar 

  43. Li SW, Arita M, Fertala A, Bao Y, Kopen GC, Langsjo TK, et al. Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility. Biochem J. 2001;355(Pt 2):271–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Fernandes RJ, Hirohata S, Engle JM, Colige A, Cohn DH, Eyre DR, et al. Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. J Biol Chem. 2001;276(34):31502–9.

    CAS  PubMed  Google Scholar 

  45. Colige A, Vandenberghe I, Thiry M, Lambert CA, Van Beeumen J, Li SW, et al. Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3. J Biol Chem. 2002;277(8):5756–66.

    CAS  PubMed  Google Scholar 

  46. Somerville RP, Longpre JM, Apel ED, Lewis RM, Wang LW, Sanes JR, et al. ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin sulfate proteoglycan containing a mucin domain. J Biol Chem. 2004;279(34):35159–75.

    CAS  PubMed  Google Scholar 

  47. Dagoneau N, Benoist-Lasselin C, Huber C, Faivre L, Megarbane A, Alswaid A, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet. 2004;75(5):801–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Somerville RP, Jungers KA, Apte SS. Discovery and characterization of a novel, widely expressed metalloprotease, ADAMTS10, and its proteolytic activation. J Biol Chem. 2004;279(49):51208–17.

    CAS  PubMed  Google Scholar 

  49. Cal S, Arguelles JM, Fernandez PL, Lopez-Otin C. Identification, characterization, and intracellular processing of ADAM-TS12, a novel human disintegrin with a complex structural organization involving multiple thrombospondin-1 repeats. J Biol Chem. 2001;276(21):17932–40.

    CAS  PubMed  Google Scholar 

  50. Porter S, Scott SD, Sassoon EM, Williams MR, Jones JL, Girling AC, et al. Dysregulated expression of adamalysin-thrombospondin genes in human breast carcinoma. Clin Cancer Res. 2004;10(7):2429–40.

    CAS  PubMed  Google Scholar 

  51. Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, et al. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004;50(1):131–41.

    CAS  PubMed  Google Scholar 

  52. Wagstaff L, Kelwick R, Decock J, Edwards DR. The roles of ADAMTS metalloproteinases in tumorigenesis and metastasis. Front Biosci (Landmark Ed). 2011;16:p. 1861–72.

    Google Scholar 

  53. Casal C, Torres-Collado AX, Plaza-Calonge Mdel C, Martino-Echarri E, Cajal Y, Ramon S, et al. ADAMTS1 contributes to the acquisition of an endothelial-like phenotype in plastic tumor cells. Cancer Res. 2010;70(11):4676–86.

    CAS  PubMed  Google Scholar 

  54. Lee NV, Sato M, Annis DS, Loo JA, Wu L, Mosher DF, et al. ADAMTS1 mediates the release of antiangiogenic polypeptides from TSP1 and 2. EMBO J. 2006;25(22):5270–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Lawler J. The functions of thrombospondin-1 and-2. Curr Opin Cell Biol. 2000;12(5):634–40.

    CAS  PubMed  Google Scholar 

  56. Nagy JA, Dvorak AM, Dvorak HF. VEGF-A and the induction of pathological angiogenesis. Annu Rev Pathol. 2007;2:251–75.

    CAS  PubMed  Google Scholar 

  57. Nagy JA, Dvorak AM, Dvorak HF. Vascular hyperpermeability, angiogenesis, and stroma generation. Cold Spring Harb Perspect Med. 2012;2(2):a006544.

    PubMed  PubMed Central  Google Scholar 

  58. Swayne GT, Smaje LH, Bergel DH. Distensibility of single capillaries and venules in the rat and frog mesentery. Int J Microcirc Clin Exp. 1989;8(1):25–42.

    CAS  PubMed  Google Scholar 

  59. Chang SH, Kanasaki K, Gocheva V, Blum G, Harper J, Moses MA, et al. VEGF-A induces angiogenesis by perturbing the cathepsin-cysteine protease inhibitor balance in venules, causing basement membrane degradation and mother vessel formation. Cancer Res. 2009;69(10):4537–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu YJ, Xu Y, Yu Q. Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively. Oncogene. 2006;25(17):2452–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Kumar S, Sharghi-Namini S, Rao N, Ge R. ADAMTS5 functions as an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity. Am J Pathol. 2012;181(3):1056–68.

    CAS  PubMed  Google Scholar 

  62. Rodriguez-Manzaneque JC, Milchanowski AB, Dufour EK, Leduc R, Iruela-Arispe ML. Characterization of METH-1/ADAMTS1 processing reveals two distinct active forms. J Biol Chem. 2000;275(43):33471–9.

    CAS  PubMed  Google Scholar 

  63. Fu Y, Nagy JA, Brown LF, Shih SC, Johnson PY, Chan CK, et al. Proteolytic cleavage of versican and involvement of ADAMTS-1 in VEGF-A/VPF-induced pathological angiogenesis. J Histochem Cytochem. 2011;59(5):463–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Nicosia RF, Tuszynski GP. Matrix-bound thrombospondin promotes angiogenesis in vitro. J Cell Biol. 1994;124(1-2):183–93.

    CAS  PubMed  Google Scholar 

  65. Tolsma SS, Volpert OV, Good DJ, Frazier WA, Polverini PJ, Bouck N. Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity. J Cell Biol. 1993;122(2):497–511.

    CAS  PubMed  Google Scholar 

  66. Jimenez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med. 2000;6(1):41–8.

    CAS  PubMed  Google Scholar 

  67. Streit M, Riccardi L, Velasco P, Brown LF, Hawighorst T, Bornstein P, et al. Thrombospondin-2: a potent endogenous inhibitor of tumor growth and angiogenesis. Proc Natl Acad Sci U S A. 1999;96(26):14888–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Lawler J, Detmar M. Tumor progression: the effects of thrombospondin-1 and -2. Int J Biochem Cell Biol. 2004;36(6):1038–45.

    CAS  PubMed  Google Scholar 

  69. Gustavsson H, Tesan T, Jennbacken K, Kuno K, Damber JE, Welen K. ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors. BMC Cancer. 2010;10:288.

    PubMed  PubMed Central  Google Scholar 

  70. Yee KO, Connolly CM, Duquette M, Kazerounian S, Washington R, Lawler J. The effect of thrombospondin-1 on breast cancer metastasis. Breast Cancer Res Treat. 2009;114(1):85–96.

    CAS  PubMed  Google Scholar 

  71. Lee YJ, Koch M, Karl D, Torres-Collado AX, Fernando NT, Rothrock C, et al. Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1. Cancer Res. 2010;70(3):948–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Vazquez F, Hastings G, Ortega MA, Lane TF, Oikemus S, Lombardo M, et al. METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. J Biol Chem. 1999;274(33):23349–57.

    CAS  PubMed  Google Scholar 

  73. Park JE, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell. 1993;4(12):1317–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Iruela-Arispe ML, Carpizo D, Luque A. ADAMTS1: a matrix metalloprotease with angioinhibitory properties. Ann N Y Acad Sci. 2003;995:183–90.

    CAS  PubMed  Google Scholar 

  75. Gupta K, Gupta P, Wild R, Ramakrishnan S, Hebbel RP. Binding and displacement of vascular endothelial growth factor (VEGF) by thrombospondin: effect on human microvascular endothelial cell proliferation and angiogenesis. Angiogenesis. 1999;3(2):147–58.

    CAS  PubMed  Google Scholar 

  76. Gengrinovitch S, Berman B, David G, Witte L, Neufeld G, Ron D. Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular chaperone for VEGF165. J Biol Chem. 1999;274(16):10816–22.

    CAS  PubMed  Google Scholar 

  77. Chen J, Zhi Y, Chang X, Zhang S, Dai D. Expression of ADAMTS1 and its correlation with angiogenesis in primary gastric cancer and lymph node metastasis. Dig Dis Sci. 2013;58(2):405–13.

    CAS  PubMed  Google Scholar 

  78. Xu Z, Yu Y, Duh EJ. Vascular endothelial growth factor upregulates expression of ADAMTS1 in endothelial cells through protein kinase C signaling. Invest Ophthalmol Vis Sci. 2006;47(9):4059–66.

    PubMed  Google Scholar 

  79. Kumar S, Rao N, Ge R. Emerging roles of ADAMTSs in angiogenesis and cancer. Cancers (Basel). 2012;4(4):1252–99.

    Google Scholar 

  80. Obika M, Ogawa H, Takahashi K, Li J, Hatipoglu OF, Cilek MZ, et al. Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis. Cancer Sci. 2012;103(10):1889–97.

    CAS  PubMed  Google Scholar 

  81. Gustavsson H, Wang W, Jennbacken K, Welen K, Damber JE. ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer. BJU Int. 2009;104(11):1786–90.

    CAS  PubMed  Google Scholar 

  82. Gustavsson H, Jennbacken K, Welen K, Damber JE. Altered expression of genes regulating angiogenesis in experimental androgen-independent prostate cancer. Prostate. 2008;68(2):161–70.

    CAS  PubMed  Google Scholar 

  83. Porter S, Span PN, Sweep FC, Tjan-Heijnen VC, Pennington CJ, Pedersen TX, et al. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma. Int J Cancer. 2006;118(5):1241–7.

    CAS  PubMed  Google Scholar 

  84. Masui T, Hosotani R, Tsuji S, Miyamoto Y, Yasuda S, Ida J, et al. Expression of METH-1 and METH-2 in pancreatic cancer. Clin Cancer Res. 2001;7(11):3437–43.

    CAS  PubMed  Google Scholar 

  85. Gendron C, Kashiwagi M, Lim NH, Enghild JJ, Thogersen IB, Hughes C, et al. Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4. J Biol Chem. 2007;282(25):18294–306.

    CAS  PubMed  Google Scholar 

  86. Sharghi-Namini S, Fan H, Sulochana KN, Potturi P, Xiang W, Chong YS, et al. The first but not the second thrombospondin type 1 repeat of ADAMTS5 functions as an angiogenesis inhibitor. Biochem Biophys Res Commun. 2008;371(2):215–9.

    CAS  PubMed  Google Scholar 

  87. El Hour M, Moncada-Pazos A, Blacher S, Masset A, Cal S, Berndt S, et al. Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis. Oncogene. 2010;29(20):3025–32.

    PubMed  Google Scholar 

  88. Llamazares M, Obaya AJ, Moncada-Pazos A, Heljasvaara R, Espada J, Lopez-Otin C, et al. The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signalling pathway. J Cell Sci. 2007;120(Pt 20):3544–52.

    CAS  PubMed  Google Scholar 

  89. Ren B, Yee KO, Lawler J, Khosravi-Far R. Regulation of tumor angiogenesis by thrombospondin-1. Biochim Biophys Acta. 2006;1765(2):178–88.

    CAS  PubMed  Google Scholar 

  90. Colige A, Ruggiero F, Vandenberghe I, Dubail J, Kesteloot F, Van Beeumen J, et al. Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V. J Biol Chem. 2005;280(41):34397–408.

    CAS  PubMed  Google Scholar 

  91. Dubail J, Kesteloot F, Deroanne C, Motte P, Lambert V, Rakic JM, et al. ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity. Cell Mol Life Sci. 2010;67(24):4213–32.

    CAS  PubMed  Google Scholar 

  92. Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem. 1998;67:395–424.

    CAS  PubMed  Google Scholar 

  93. Ruggeri ZM. The role of von Willebrand factor in thrombus formation. Thromb Res. 2007;120 Suppl 1:S5–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488–94.

    CAS  PubMed  Google Scholar 

  95. Starke RD, Ferraro F, Paschalaki KE, Dryden NH, McKinnon TA, Sutton RE, et al. Endothelial von Willebrand factor regulates angiogenesis. Blood. 2011;117(3):1071–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Hodivala-Dilke K. alphavbeta3 integrin and angiogenesis: a moody integrin in a changing environment. Curr Opin Cell Biol. 2008;20(5):p. 514–9.

    Google Scholar 

  97. Hodivala-Dilke KM, Reynolds AR, Reynolds LE. Integrins in angiogenesis: multitalented molecules in a balancing act. Cell Tissue Res. 2003;314(1):131–44.

    CAS  PubMed  Google Scholar 

  98. Dalton SL, Scharf E, Briesewitz R, Marcantonio EE, Assoian RK. Cell adhesion to extracellular matrix regulates the life cycle of integrins. Mol Biol Cell. 1995;6(12):1781–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Yu Q, Stamenkovic I. Angiopoietin-2 is implicated in the regulation of tumor angiogenesis. Am J Pathol. 2001;158(2):563–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Hashizume H, Falcon BL, Kuroda T, Baluk P, Coxon A, Yu D, et al. Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth. Cancer Res. 2010;70(6):2213–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Thomas M, Felcht M, Kruse K, Kretschmer S, Deppermann C, Biesdorf A, et al. Angiopoietin-2 stimulation of endothelial cells induces alphavbeta3 integrin internalization and degradation. J Biol Chem. 2010;285(31):23842–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Lee M, Rodansky ES, Smith JK, Rodgers GM. ADAMTS13 promotes angiogenesis and modulates VEGF-induced angiogenesis. Microvasc Res. 2012;84(2):109–15.

    CAS  PubMed  Google Scholar 

  103. Koo BH, Coe DM, Dixon LJ, Somerville RP, Nelson CM, Wang LW, et al. ADAMTS9 is a cell-autonomously acting, anti-angiogenic metalloprotease expressed by microvascular endothelial cells. Am J Pathol. 2010;176(3):1494–504.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Kelwick R, Wagstaff L, Decock J, Roghi C, Cooley LS, Robinson SD, et al. Metalloproteinase-dependent and -independent processes contribute to inhibition of breast cancer cell migration, angiogenesis and liver metastasis by a disintegrin and metalloproteinase with thrombospondin motifs-15. Int J Cancer. 2015;136(4):E14–26.

    CAS  PubMed  Google Scholar 

  105. Nissinen L, Kahari VM. ADAMTS5: a new player in the vascular field. Am J Pathol. 2012;181(3):743–5.

    CAS  PubMed  Google Scholar 

  106. Saharinen P, Eklund L, Pulkki K, Bono P, Alitalo K. VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med. 2011;17(7):347–62.

    CAS  PubMed  Google Scholar 

  107. Rao N, Ke Z, Liu H, Ho CJ, Kumar S, Xiang W, et al. ADAMTS4 and its proteolytic fragments differentially affect melanoma growth and angiogenesis in mice. Int J Cancer. 2013;133(2):294–306.

    CAS  PubMed  Google Scholar 

  108. Keightley M, Sales K, Jabbour H. PGF2alpha-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer. BMC Cancer. 2010;10(1):488.

    PubMed  PubMed Central  Google Scholar 

  109. Hsu YP, Staton CA, Cross N, Buttle DJ. Anti-angiogenic properties of ADAMTS-4 in vitro. Int J Exp Pathol. 2012;93(1):70–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Karagiannis ED, Popel AS. Anti-angiogenic peptides identified in thrombospondin type I domains. Biochem Biophys Res Commun. 2007;359(1):63–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Lo PHY, Lung HL, Cheung AKL, Apte SS, Chan KW, Kwong FM, et al. Extracellular protease ADAMTS9 Suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis. Cancer Res. 2010;70(13):5567–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Kuno K, Bannai K, Hakozaki M, Matsushima K, Hirose K. The carboxyl-terminal half region of ADAMTS-1 suppresses both tumorigenicity and experimental tumor metastatic potential. Biochem Biophys Res Commun. 2004;319(4):1327–33.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported partly by The Science and Technology Planning Project of Guangdong Province (No. 2013B02180), China.

Conflict of interests

None.

Author information

Author notes

    Authors and Affiliations

    1. Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China

      Yi Sun, Jintuan Huang & Zuli Yang

    Authors
    1. Yi Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jintuan Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Zuli Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Zuli Yang.

    Additional information

    Yi Sun and Jintuan Huang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Sun, Y., Huang, J. & Yang, Z. The roles of ADAMTS in angiogenesis and cancer. Tumor Biol. 36, 4039–4051 (2015). https://doi.org/10.1007/s13277-015-3461-8

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-015-3461-8

    Keywords

    Search

    Navigation