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More than a Scaffold: Extracellular Matrix in Vascular Signaling

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Endothelial Signaling in Development and Disease

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Abstract

Extracellular matrix (ECM), a non-living material that fills the space surrounding the cells, plays critical functions in multicellular organisms. On a macroscopic level, a complex mixture of proteins and polysaccharides organized in fibers and mesh-like structures provides biomechanical support to tissues, and defines organ shape and dimensions. However, on a microscopic level ECM is not just a structural element of the cellular environment but an important communication medium between the cells and their surroundings, as well as between the cells themselves. Physiological processes during embryonic development and in the adult require cells to perform their basic functions, such as survival and death, multiplication and migration, and a complex repertoire of matrix proteins and receptors helps the cells attune to the changes in their local setting. However, ECM is also a dynamic system that undergoes constant remodeling, and when that process goes awry it can promote and facilitate numerous pathological conditions. This chapter will explore how this intricate milieu of structurally and functionally divergent molecules regulates endothelial cell biology in health and disease.

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References

  1. Schaefer L, Schaefer RM. Proteoglycans: from structural compounds to signaling molecules. Cell Tissue Res. 2010;339:237–46. doi:10.1007/s00441-009-0821-y.

    Article  CAS  PubMed  Google Scholar 

  2. Wight TN. Cell biology of arterial proteoglycans. Arteriosclerosis. 1989;9:1–20.

    Article  CAS  PubMed  Google Scholar 

  3. Iozzo RV. Basement membrane proteoglycans: from cellar to ceiling. Nat Rev Mol Cell Biol. 2005;6:646–56. doi:nrm1702 [pii]10.1038/nrm1702.

    Article  CAS  PubMed  Google Scholar 

  4. Couchman JR, Pataki CA. An introduction to proteoglycans and their localization. J Histochem Cytochem. 2012;60:885–97. doi:10.1369/0022155412464638.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Rozario T, DeSimone DW. The extracellular matrix in development and morphogenesis: a dynamic view. Dev Biol. 2010;341:126–40. doi:S0012-1606(09)01285-8 [pii]10.1016/j.ydbio.2009.10.026.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Muiznieks LD, Keeley FW. Molecular assembly and mechanical properties of the extracellular matrix: a fibrous protein perspective. Biochim Biophys Acta. 2013;1832:866–75. doi:S0925-4439(12)00283-9 [pii]10.1016/j.bbadis.2012.11.022.

    Article  CAS  PubMed  Google Scholar 

  7. Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev. 2009;89:957–89. doi:89/3/957 [pii]10.1152/physrev.00041.2008.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Kielty CM, Sherratt MJ, Shuttleworth CA. Elastic fibres. J Cell Sci. 2002;115:2817–28.

    CAS  PubMed  Google Scholar 

  9. Kostourou V, Papalazarou V. Non-collagenous ECM proteins in blood vessel morphogenesis and cancer. Biochim Biophys Acta. 2014;2014(02):018. doi:S0304-4165.1400079 8 pii101016jbbagen.

    Google Scholar 

  10. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123:4195–4200. doi:123/24/4195 [pii]10.1242/jcs.023820.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Smith ML. et al. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol. 2007;5:e268. doi:07-PLBI-RA-0149 [pii]10.1371/journal.pbio.0050268.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Bornstein P, Sage EH. Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol. 2002;14:608–16. doi:S0955067402003617 [pii].

    Article  CAS  PubMed  Google Scholar 

  13. Nikolic I, Plate KH, Schmidt MH. EGFL7 meets miRNA-126: an angiogenesis alliance. J Angiogenesis Res. 2010;2:9. doi:10.1186/2040-2384-2-9.

    Article  CAS  Google Scholar 

  14. Werneck CC, et al. Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury. Blood. 2008;111:4137–44. doi:10.1182/blood-2007-07-101733.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Bradshaw AD, et al. SPARC-null mice display abnormalities in the dermis characterized by decreased collagen fibril diameter and reduced tensile strength. J Invest Dermatol. 2003;120:949–55. doi:12241 [pii]101046j15231747200312241x.

    Article  CAS  PubMed  Google Scholar 

  16. Rios H, et al. periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol. 2005;25:11131–44. doi:25/24/11131 [pii]10.1128/MCB.25.24.11131–11144.2005.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Chiodoni C, Colombo MP, Sangaletti S. Matricellular proteins: from homeostasis to inflammation, cancer, and metastasis. Cancer Metastasis Rev. 2010;29:295–307. doi:10.1007/s10555-010-9221-8.

    Article  CAS  PubMed  Google Scholar 

  18. Wong GS, Rustgi AK. Matricellular proteins: priming the tumour microenvironment for cancer development and metastasis. Br J Cancer. 2013;108:755–61. doi:bjc2012592 [pii]10.1038/bjc.2012.592.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Bellon G, Martiny L, Robinet A. Matrix metalloproteinases and matrikines in angiogenesis. Crit Rev Oncol Hematol. 2004;49:203–20. doi:101016jcritrevonc200310004 S1040842803002762 [pii].

    Article  PubMed  Google Scholar 

  20. Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326:1216–19. doi:326/5957/1216 [pii]10.1126/science.1176009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002;2:91–100. doi:10.1038/nrc727.

    Article  PubMed  Google Scholar 

  22. Stupack DG, Cheresh DA. ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci STKE. 2002. doi:10.1126/stke.2002.119.pe72002/119/pe72002/119/pe7 [pii].

    Google Scholar 

  23. Tkachenko E, Rhodes JM, Simons M. Syndecans: new kids on the signaling block. Circ Res. 2005;96:488–500. doi:96/5/488 [pii]10.1161/01.RES.0000159708.71142.c8.

    Article  CAS  PubMed  Google Scholar 

  24. Hosokawa H, Ninomiya H, Kitamura Y, Fujiwara K, Masaki T. Vascular endothelial cells that express dystroglycan are involved in angiogenesis. J Cell Sci. 2002;115:1487–96.

    CAS  PubMed  Google Scholar 

  25. Flamme I, Risau W. Induction of vasculogenesis and hematopoiesis in vitro. Development. 1992;116:435–9.

    CAS  PubMed  Google Scholar 

  26. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6:389–95. doi:10.1038/74651.

    Article  CAS  PubMed  Google Scholar 

  27. Herbert SP, Stainier DY. Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat Rev. Mol Cell Biol. 2011;12:551–64. doi:nrm3176 [pii]10.1038/nrm3176.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Nitta T, et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol. 2003;161:653–60. doi:10.1083/jcb.200302070jcb.200302070 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Corada M, et al. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci U S A. 1999;96:9815–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Darland DC, D'Amore PA. Blood vessel maturation: vascular development comes of age. J Clin Invest. 1999;103:157–8. doi:10.1172/JCI6127.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Myers C, Charboneau A, Cheung I, Hanks D, Boudreau N. Sustained expression of homeobox D10 inhibits angiogenesis. Am J Pathol. 2002;161:2099–109. doi:S0002-9440(10)64488-4 [pii]10.1016/S0002-9440(10)64488-4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Rhoads K, et al. A role for Hox A5 in regulating angiogenesis and vascular patterning. Lymphat Res Biol. 2005;3:240–52. doi:10.1089/lrb.2005.3.240.

    Article  CAS  PubMed  Google Scholar 

  33. Stoll SJ, Bartsch S, Augustin HG, Kroll J. The transcription factor HOXC9 regulates endothelial cell quiescence and vascular morphogenesis in zebrafish via inhibition of interleukin 8. Circ Res. 2011;108:1367–77. doi:CIRCRESAHA.111.244095 [pii]10.1161/CIRCRESAHA.111.244095.

    Article  CAS  PubMed  Google Scholar 

  34. Patel S, Leal AD, Gorski DH. The homeobox gene Gax inhibits angiogenesis through inhibition of nuclear factor-kappaB-dependent endothelial cell gene expression. Cancer Res. 2005;65:1414–1424. doi:65/4/1414 [pii]10.1158/0008-5472.CAN-04-3431.

    Article  CAS  PubMed  Google Scholar 

  35. Potter MD, Barbero S, Cheresh DA. Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state. J Biol Chem. 2005;280:31906–12. doi:M505568200 [pii]10.1074/jbc.M505568200.

    Article  CAS  PubMed  Google Scholar 

  36. Chen XL, et al. VEGF-induced vascular permeability is mediated by FAK. Dev Cell. 2012;22:146–57. doi:S1534-5807(11)00512-0 [pii]10.1016/j.devcel.2011.11.002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Boudreau N, Andrews C, Srebrow A, Ravanpay A, Cheresh DA. Induction of the angiogenic phenotype by Hox D3. J Cell Biol. 1997;139:257–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Diehl F, Rossig L, Zeiher AM, Dimmeler S, Urbich C. The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation. Blood. 2007;109:1472–78. doi:blood-2006-08-039651 [pii]10.1182/blood-2006-08-039651.

    Article  CAS  PubMed  Google Scholar 

  39. Myers C, Charboneau A, Boudreau N. Homeobox B3 promotes capillary morphogenesis and angiogenesis. J Cell Biol. 2000;148:343–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Estrach S, et al. Laminin-binding integrins induce Dll4 expression and Notch signaling in endothelial cells. Circ Res. 2011;109:172–82. doi:CIRCRESAHA.111.240622 [pii]10.1161/CIRCRESAHA.111.240622.

    Article  CAS  PubMed  Google Scholar 

  41. Stenzel D, et al. Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Rep. 2011;12:1135–43. doi:embor2011194 [pii]10.1038/embor.2011.194.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. del Toro R, et al. Identification and functional analysis of endothelial tip cell-enriched genes. Blood. 2010;116:4025–33. doi:blood-2010-02-270819 [pii]10.1182/blood-2010-02-270819.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Nichol D, et al. Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7. Blood. 2010;116:6133–43. doi:10.1182/blood-2010-03-274860.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Schmidt MH, et al. Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal. Nat Cell Biol. 2009;11:873–80. doi:10.1038/ncb1896.

    Article  CAS  PubMed  Google Scholar 

  45. Albig AR, Becenti DJ, Roy TG, Schiemann WP. Microfibril-associate glycoprotein-2 (MAGP-2) promotes angiogenic cell sprouting by blocking notch signaling in endothelial cells. Microvasc Res. 2008;76:7–14. doi:10.1016/j.mvr.2008.01.001.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem. 1992;267:26031–7.

    CAS  PubMed  Google Scholar 

  47. Otrock ZK, Mahfouz RA, Makarem JA, Shamseddine AI. Understanding the biology of angiogenesis: review of the most important molecular mechanisms. Blood Cells Mol Dis. 2007;39:212–20. doi:S1079-9796(07)00077-0 [pii]10.1016/j.bcmd.2007.04.001.

    Article  CAS  PubMed  Google Scholar 

  48. Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol. 2001;21:1104–17.

    Article  CAS  PubMed  Google Scholar 

  49. Senger DR, et al. The alpha(1)beta(1) and alpha(2)beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am J Pathol. 2002;160:195–204. doi:S0002-9440(10)64363-5 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Klemke RL, et al. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol. 1997;137:481–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007;100:782–94. doi:100/6/782 [pii]10116101RES0000259593076611e.

    Article  CAS  PubMed  Google Scholar 

  52. De Smet F, Segura I, De Bock K, Hohensinner PJ, Carmeliet P. Mechanisms of vessel branching: filopodia on endothelial tip cells lead the way. Arterioscler Thromb Vasc Biol. 2009;29:639–49. doi:ATVBAHA.109.185165 [pii]10.1161/ATVBAHA.109.185165.

    Article  PubMed  CAS  Google Scholar 

  53. Dallas SL, Chen Q, Sivakumar P. Dynamics of assembly and reorganization of extracellular matrix proteins. Curr Topics Dev Biol. 2006;75:1–24. doi:10.1016/S0070-2153(06)75001-3.

    Article  CAS  Google Scholar 

  54. Murphy-Ullrich JE, Hook M. Thrombospondin modulates focal adhesions in endothelial cells. J Cell Biol. 1989;109:1309–19.

    Article  CAS  PubMed  Google Scholar 

  55. Murphy-Ullrich JE, et al. Focal adhesion integrity is downregulated by the alternatively spliced domain of human tenascin. J Cell Biol. 1991;115:1127–36.

    Article  CAS  PubMed  Google Scholar 

  56. Greenwood JA, Murphy-Ullrich JE. Signaling of de-adhesion in cellular regulation and motility. Microsc Res Tech. 1998;43:420–32. doi:10.1002/(SICI)1097-0029(19981201)43:5<420::AID-JEMT8>3.0.CO;2-B [pii]10.1002/(SICI)1097-0029(19981201)43:5<420::AID-JEMT8>3.0.CO;2-B.

    Article  CAS  PubMed  Google Scholar 

  57. DiMilla PA, Barbee K, Lauffenburger DA Mathematical model for the effects of adhesion and mechanics on cell migration speed. Biophys J. 1991;60:15–37. doi:S0006-3495(91)82027-6 [pii]10.1016/S0006-3495(91)82027–6.

    Google Scholar 

  58. Palecek SP, Loftus JC, Ginsberg MH, Lauffenburger DA, Horwitz AF. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature. 1997;385:537–40. doi:10.1038/385537a0.

    Article  CAS  PubMed  Google Scholar 

  59. Nikolic I, et al. EGFL7 ligates alphavbeta3 integrin to enhance vessel formation. Blood. 2013;121:3041–50. doi:blood-2011-11-394882 [pii]10.1182/blood-2011-11-394882.

    Article  CAS  PubMed  Google Scholar 

  60. Murphy-Ullrich JE. The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state? J Clin Invest. 2001;107:785–90. doi:10.1172/JCI12609.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Phng LK, et al. Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Dev Cell. 2009;16:70–82. doi:S1534-5807(08)00519-4 [pii]10.1016/j.devcel.2008.12.009.

    Article  CAS  PubMed  Google Scholar 

  62. Phng LK, Gerhardt H. Angiogenesis: a team effort coordinated by notch. Dev Cell. 2009;16:196–208. doi:S1534-5807(09)00043-4 [pii]10.1016/j.devcel.2009.01.015.

    Article  CAS  PubMed  Google Scholar 

  63. Wary KK, Mainiero F, Isakoff SJ, Marcantonio EE, Giancotti FG. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell. 1996;87:733–43. doi:S0092-8674(00)81392-6 [pii].

    Article  CAS  PubMed  Google Scholar 

  64. Roovers K, Assoian RK. Integrating the MAP kinase signal into the G1 phase cell cycle machinery. Bioessays. 2000;22:818–26. doi:10.1002/1521-1878(200009)22:9<818::AID-BIES7>3.0.CO;2-6 [pii]10.1002/1521-1878(200009)22:9<818::AID-BIES7>3.0.CO;2-6.

    Article  CAS  PubMed  Google Scholar 

  65. Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J. 1997;16:2783–93. doi:10.1093/emboj/16.10.2783.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Ilic D, et al. Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J Cell Biol. 1998;143:547–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Meredith JE Jr, Schwartz MA. Integrins, adhesion and apoptosis. Trends Cell Biol. 1997;7:146–50. doi:S0962-8924(97)01002-7 [pii]10.1016/S0962-8924(97)01002-7.

    Article  CAS  PubMed  Google Scholar 

  68. Bayless KJ, Davis GE. Sphingosine-1-phosphate markedly induces matrix metalloproteinase and integrin-dependent human endothelial cell invasion and lumen formation in three-dimensional collagen and fibrin matrices. Biochem Biophys Res Commun. 2003;312:903–13.doi:S0006291X03023659 [pii].

    Article  CAS  PubMed  Google Scholar 

  69. Gerhardt H, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161:1163–77. doi:10.1083/jcb.200302047jcb.200302047 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Davis GE, Koh W, Stratman AN. Mechanisms controlling human endothelial lumen formation and tube assembly in three-dimensional extracellular matrices. Birth Defects Res C Embryo Today. 2007;81:270–85. doi:10.1002/bdrc.20107.

    Article  CAS  PubMed  Google Scholar 

  71. Davis GE, Camarillo CW. An alpha 2 beta 1 integrin-dependent pinocytic mechanism involving intracellular vacuole formation and coalescence regulates capillary lumen and tube formation in three-dimensional collagen matrix. Exp Cell Res. 1996;224:39–51. doi:S0014-4827(96)90109-3 [pii]10.1006/excr.1996.0109.

    Article  CAS  PubMed  Google Scholar 

  72. Kamei M, et al. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature. 2006;442: 453–456. doi:nature04923 [pii]10.1038/nature04923.

    Article  CAS  PubMed  Google Scholar 

  73. Blum Y, et al. Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo. Dev Biol. 2008;316:312–22. doi:S0012-1606(08)00079-1 [pii]10.1016/j.ydbio.2008.01.038.

    Article  CAS  PubMed  Google Scholar 

  74. Strilic B, et al. The molecular basis of vascular lumen formation in the developing mouse aorta. Dev Cell. 2009;17:505–15. doi:S1534-5807(09)00349-9 [pii]10.1016/j.devcel.2009.08.011.

    Article  CAS  PubMed  Google Scholar 

  75. Whelan MC, Senger DR. Collagen I initiates endothelial cell morphogenesis by inducing actin polymerization through suppression of cyclic AMP and protein kinase A. J Biol Chem. 2003;278:327–34. doi:10.1074/jbc.M207554200M207554200 [pii].

    Article  CAS  PubMed  Google Scholar 

  76. Liu Y, Senger DR. Matrix-specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells. FASEB J. 2004;18:457–68. doi:10.1096/fj.03-0948com18/3/457 [pii].

    Article  CAS  PubMed  Google Scholar 

  77. Drake CJ, Davis LA, Little CD. Antibodies to beta 1-integrins cause alterations of aortic vasculogenesis, in vivo. Dev Dyn. 1992;193:83–91. doi:10.1002/aja.1001930111.

    Article  CAS  PubMed  Google Scholar 

  78. Zovein AC, et al. Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Dev Cell. 2010;18:39–51. doi:S1534-5807(09)00488-2 [pii]10.1016/j.devcel.2009.12.006.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Bayless KJ, Salazar R, Davis GE. RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the alpha(v)beta(3) and alpha(5)beta(1) integrins. Am J Pathol. 2000;156:1673–83. doi:S0002-9440(10)65038-9 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Koh W, Mahan RD, Davis GE. Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling. J Cell Sci. 2008;121:989–1001. doi:jcs.020693 [pii]10.1242/jcs.020693.

    Article  CAS  PubMed  Google Scholar 

  81. Parker LH, et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature. 2004;428:754–8. doi:10.1038/nature02416nature02416 [pii].

    Article  CAS  PubMed  Google Scholar 

  82. Charpentier MS, et al. CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7/RhoA-mediated pathway. Dev Cell. 2013;25:132–43. doi:S1534-5807(13)00134-2 [pii]10.1016/j.devcel.2013.03.003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Jakobsson L, Domogatskaya A, Tryggvason K, Edgar D, Claesson-Welsh L. Laminin deposition is dispensable for vasculogenesis but regulates blood vessel diameter independent of flow. FASEB J. 2008;22:1530–9. doi:fj.07-9617com [pii]101096fj07-9617com.

    Article  CAS  PubMed  Google Scholar 

  84. Jain RK. Molecular regulation of vessel maturation. Nat Med. 2003;9:685–93. doi:10.1038/nm0603-685 [pii]nm0603-685 [pii].

    Article  CAS  PubMed  Google Scholar 

  85. Stratman AN, Malotte KM, Mahan RD, Davis MJ, Davis GE. Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood. 2009;114:5091–101. doi:blood-2009-05-222364 [pii]10.1182/blood-2009-05-222364.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Zhou Z, et al. Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice. Cancer Res. 2004;64:4059–63. doi:10.1158/0008-5472.CAN-04-029164/12/4059 [pii].

    Article  CAS  PubMed  Google Scholar 

  87. Li Q, Olsen BR. Increased angiogenic response in aortic explants of collagen XVIII/endostatin-null mice. Am J Pathol. 2004;165:415–24. doi:S0002-9440(10)63307-X [pii]10.1016/S0002-9440(10)63307–X.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Mettouchi A, et al. Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. Mol Cell. 2001;8:115–27. doi:S1097-2765(01)00285-4 [pii].

    Article  CAS  PubMed  Google Scholar 

  89. Klein S, et al. Alpha 5 beta 1 integrin activates an NF-kappa B-dependent program of gene expression important for angiogenesis and inflammation. Mol Cell Biol. 2002;22:5912–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Hall-Glenn F, et al. CCN2/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis. PLoS One. 2012;7:e30562. doi:10.1371/journal.pone.0030562PONE-D-11-19485 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Yamaguchi N, et al. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EMBO J. 1999;18:4414–23. doi:10.1093/emboj/18.16.4414.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Taddei L, et al. Inhibitory effect of full-length human endostatin on in vitro angiogenesis. Biochem Biophys Res Commun. 1999;263:340–5. doi:10.1006/bbrc.1999.1342S0006-291X(99)91342-6 [pii].

    Article  CAS  PubMed  Google Scholar 

  93. Pasco S, et al. A specific sequence of the noncollagenous domain of the alpha3(IV) chain of type IV collagen inhibits expression and activation of matrix metalloproteinases by tumor cells. Cancer Res. 2000;60:467–73.

    CAS  PubMed  Google Scholar 

  94. Adams JC. Thrombospondins: multifunctional regulators of cell interactions. Annu Rev Cell Dev Biol. 2001;17:25–51. doi:10.1146/annurev.cellbio.17.1.2517/1/25 [pii].

    Article  CAS  PubMed  Google Scholar 

  95. Bornstein P. Thrombospondins as matricellular modulators of cell function. J Clin Invest. 2001;107:929–34. doi:10.1172/JCI12749.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  PubMed  Google Scholar 

  97. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.

    Article  CAS  PubMed  Google Scholar 

  98. Morikawa S, et al. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol. 2002;160:985–1000. doi:10.1016/S0002-9440(10)64920-6.

    Article  PubMed Central  PubMed  Google Scholar 

  99. Weis SM, Cheresh DA. Pathophysiological consequences of VEGF-induced vascular permeability. Nature. 2005;437:497–504. doi:10.1038/nature03987.

    Article  CAS  PubMed  Google Scholar 

  100. Bergers G, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2:737–44. doi:10.1038/35036374.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Foley CJ, et al. Matrix metalloprotease 1a deficiency suppresses tumor growth and angiogenesis. Oncogene. 2014;33:2264–72. doi:onc2013157 [pii]10.1038/onc.2013.157.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Nakamura T, et al. Stromal metalloproteinase-9 is essential to angiogenesis and progressive growth of orthotopic human pancreatic cancer in parabiont nude mice. Neoplasia. 2007;9:979–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Maity G, et al. Pancreatic tumor cell secreted CCN1/Cyr61 promotes endothelial cell migration and aberrant neovascularization. Sci Rep. 2014;4:4995. doi:srep04995 [pii]10.1038/srep04995.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Johnson L, et al. Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy. J Clin Investg. 2013;123:3997–4009. doi:67892 [pii]10.1172/JCI67892.

    Article  CAS  Google Scholar 

  105. Kauppila S, Stenback F, Risteli J, Jukkola A, Risteli L. Aberrant type I and type III collagen gene expression in human breast cancer in vivo. J Pathol. 1998;186:262–8. doi:10.1002/(SICI)1096-9896(1998110)186:3<262::AID-PATH191>3.0.CO;2-3 [pii]10.1002/(SICI)1096-9896(1998110)186:3<262::AID-PATH191>3.0.CO;2-3.

    Article  CAS  PubMed  Google Scholar 

  106. Yeh YT, et al. Matrix stiffness regulates endothelial cell proliferation through septin 9. PLoS One. 2012;7:e46889. doi:10.1371/journal.pone.0046889PONE-D-12-16147 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  107. Seaman S, et al. Genes that distinguish physiological and pathological angiogenesis. Cancer Cell. 2007;11:539–54. doi:S1535-6108(07)00144-4 [pii]10.1016/j.ccr.2007.04.017.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  108. Tanaka K, Hiraiwa N, Hashimoto H, Yamazaki Y, Kusakabe M. Tenascin-C regulates angiogenesis in tumor through the regulation of vascular endothelial growth factor expression. Int J Cancer. 2004;108:31–40. doi:10.1002/ijc.11509.

    Article  CAS  PubMed  Google Scholar 

  109. Schenk S, Chiquet-Ehrismann R, Battegay EJ. The fibrinogen globe of tenascin-C promotes basic fibroblast growth factor-induced endothelial cell elongation. Mol Biol Cell. 1999;10:2933–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Brooks PC, et al. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994;79:1157–64. doi:0092-8674(94)90007-8 [pii].

    Article  CAS  PubMed  Google Scholar 

  111. Kim S, Harris M, Varner JA. Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A. J Biol Chem. 2000;275:33920–8. doi:10.1074/jbc.M003668200.

    Article  CAS  PubMed  Google Scholar 

  112. Senger DR, et al. Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Proc Natl Acad Sci U S A. 1997;94:13612–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  113. Zhang Z, et al. alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner. Blood. 2008;111:1980–8. doi:blood-2007-06-094680 [pii]10.1182/blood-2007-06-094680.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  114. Reynolds LE, et al. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med. 2002;8:27–34. doi:10.1038/nm0102-27nm0102-27 [pii].

    Article  CAS  PubMed  Google Scholar 

  115. Steri V, et al. Acute depletion of endothelial beta3-integrin transiently inhibits tumor growth and angiogenesis in mice. Circ Res. 2014;114:79–91. doi:CIRCRESAHA.114.301591 [pii]10.1161/CIRCRESAHA.114.301591.

    Article  CAS  PubMed  Google Scholar 

  116. Shi Q, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998;92:362–7.

    CAS  PubMed  Google Scholar 

  117. Asahara T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.

    Article  CAS  PubMed  Google Scholar 

  118. Patenaude A, Parker J, Karsan A. Involvement of endothelial progenitor cells in tumor vascularization. Microvasc Res. 2010;79:217–23. doi:10.1016/j.mvr.2010.01.007.

    Article  CAS  PubMed  Google Scholar 

  119. Gao D, et al. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 2008;319:195–98. doi:319/5860/195 [pii]10.1126/science.1150224.

    Article  CAS  PubMed  Google Scholar 

  120. Nolan DJ, et al. Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization. Genes Dev. 2007;21:1546–58. doi:21/12/1546 [pii]10.1101/gad.436307.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. Bouvard C, et al. alpha6-integrin subunit plays a major role in the proangiogenic properties of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2010;30:1569–75. doi:ATVBAHA.110.209163 [pii]10.1161/ATVBAHA.110.209163.

    Article  CAS  PubMed  Google Scholar 

  122. Caiado F, Dias S. Endothelial progenitor cells and integrins: adhesive needs. Fibrogenesis Tissue Repair. 2012;5:4. doi:1755-1536-5-4 [pii]10.1186/1755-1536-5-4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  123. Walter DH, et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002;105:3017–24.

    Article  CAS  PubMed  Google Scholar 

  124. Kokubo T, Uchida H, Choi ET. Integrin alpha(v)beta(3) as a target in the prevention of neointimal hyperplasia. J Vasc Surg. 2007;45 Suppl A:A33–8. doi:S0741-5214(07)00422-3 [pii]10.1016/j.jvs.2007.02.069.

    Article  PubMed  Google Scholar 

  125. Di Santo S, et al. Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5. Biochem Biophys Res Commun. 2008;373:528–32. doi:S0006-291X(08)01213-8 [pii]10.1016/j.bbrc.2008.06.066.

    Article  CAS  PubMed  Google Scholar 

  126. Igreja C, et al. Detailed molecular characterization of cord blood-derived endothelial progenitors. Exp Hematol. 2008;36:193–203. doi:S0301-472X(07)00558-9 [pii]10.1016/j.exphem.2007.09.001.

    Article  CAS  PubMed  Google Scholar 

  127. Wijelath ES, et al. Fibronectin promotes VEGF-induced CD34 cell differentiation into endothelial cells. J Vasc Surg. 2004;39:655–60. doi:10.1016/j.jvs.2003.10.042.

    Article  PubMed  Google Scholar 

  128. Yu Y, et al. CCN1 promotes the differentiation of endothelial progenitor cells and reendothelialization in the early phase after vascular injury. Basic Res Cardiol. 105:713–724. doi:10.1007/s00395-010-0117-0(2010).

    Google Scholar 

  129. Caiado F, et al. The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing. Biomaterials. 2011;32:7096–105. doi:S0142-9612(11)00687-9 [pii]10.1016/j.biomaterials.2011.06.022.

    Article  CAS  PubMed  Google Scholar 

  130. Wang R, et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 2010;468:829–33. doi:nature09624 [pii]10.1038/nature09624.

    Article  CAS  PubMed  Google Scholar 

  131. Ricci-Vitiani L, et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature. 2010;468:824–8. doi:nature09557 [pii]10.1038/nature09557.

    Article  CAS  PubMed  Google Scholar 

  132. McGuire TF, Sajithlal GB, Lu J, Nicholls RD, Prochownik EV. In vivo evolution of tumor-derived endothelial cells. PLoS One. 2012;7:e37138. doi:10.1371/journal.pone.0037138PONE-D-12-03955 [pii].

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  133. Maniotis AJ, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 1999;155:739–52. doi:10.1016/S0002-9440(10)65173-5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  134. Shirakawa K, et al. Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. Cancer Res. 2001;61:445–51.

    CAS  PubMed  Google Scholar 

  135. Sood AK, et al. The clinical significance of tumor cell-lined vasculature in ovarian carcinoma: implications for anti-vasculogenic therapy. Cancer Biol Ther. 2002;1:661–4. doi:316 [pii].

    Article  PubMed  Google Scholar 

  136. van der Schaft DW, et al. Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia. Cancer Res. 2005;65:11520–8. doi:65/24/11520 [pii]10.1158/0008-5472.CAN-05-2468.

    Article  PubMed  CAS  Google Scholar 

  137. Watt FM, Huck WT. Role of the extracellular matrix in regulating stem cell fate. Nat Rev Mol Cell Biol. 2013;14:467–73. doi:10.1038/nrm3620.

    Article  CAS  PubMed  Google Scholar 

  138. Pezzolo A, et al. Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells. Cell Res. 2011;21:1470–86. doi:10.1038/cr.2011.38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  139. Mourad-Zeidan AA, Melnikova VO, Wang H, Raz A, Bar-Eli M. Expression profiling of Galectin-3-depleted melanoma cells reveals its major role in melanoma cell plasticity and vasculogenic mimicry. Am J Pathol. 2008;173:1839–52. doi:S0002-9440(10)61567-2 [pii]10.2353/ajpath.2008.080380.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  140. Seftor EA, et al. Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment. Cancer Res. 2005;65:10164–9. doi:65/22/10164 [pii]10.1158/0008-5472.CAN-05-2497.

    Article  CAS  PubMed  Google Scholar 

  141. Seftor RE, et al. Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res. 2001;61:6322–7.

    CAS  PubMed  Google Scholar 

  142. Goodman SL, Picard M. Integrins as therapeutic targets. Trends Pharmacol Sci. 2012;33:405–12. doi:S0165-6147(12)00057-0 [pii]10.1016/j.tips.2012.04.002.

    Article  CAS  PubMed  Google Scholar 

  143. Bach-Gansmo T, et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692. J Nucl Med. 2006;47:1434–9. doi:47/9/1434 [pii].

    CAS  PubMed  Google Scholar 

  144. Cheresh DA, Stupack DG. Tumor angiogenesis: putting a value on plastic GEMMs. Circ Res. 2014;114:9–11. doi:CIRCRESAHA.113.302812 [pii]10.1161/CIRCRESAHA.113.302812.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  145. Reynolds AR, et al. Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med. 2009;15:392–400. doi:nm.1941 [pii]10.1038/nm.1941.

    Article  CAS  PubMed  Google Scholar 

  146. Dornhofer N, et al. Connective tissue growth factor-specific monoclonal antibody therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2006;66:5816–27. doi:66/11/5816 [pii]10.1158/0008-5472.CAN-06-0081.

    Article  PubMed  Google Scholar 

  147. Neri D, Bicknell R. Tumour vascular targeting. Nat Rev Cancer. 2005;5:436–46. doi:nrc1627 [pii]10.1038/nrc1627.

    Article  CAS  PubMed  Google Scholar 

  148. Ghajar CM, et al. The perivascular niche regulates breast tumour dormancy. Nat Cell Biol. 2013;15:807–17. doi:ncb2767 [pii]10.1038/ncb2767.

    Article  CAS  PubMed  Google Scholar 

  149. Boyerinas B, et al. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood. 2013;121:4821–31. doi:blood-2012-12-475483 [pii]10.1182/blood-2012-12-475483.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  150. Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP. Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features. Cancer Res. 2001;61:8917–23.

    CAS  PubMed  Google Scholar 

  151. Tian C, et al. Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients. World J Gastroenterol. 2007;13:3878–82.

    Article  CAS  PubMed  Google Scholar 

  152. Hashimoto Y, et al. Expression of the Elm1 gene, a novel gene of the CCN (connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses In vivo tumor growth and metastasis of K-1735 murine melanoma cells. J Exp Med. 1998;187:289–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  153. Gupta N, et al. Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV). Mol Pathol. 2001;54:293–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  154. Vallacchi V, et al. CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. Cancer Res. 2008;68:715–23. doi:68/3/715 [pii]10.1158/0008-5472.CAN-07-2103.

    Article  CAS  PubMed  Google Scholar 

  155. Shevde LA, Das S, Clark DW, Samant RS. Osteopontin: an effector and an effect of tumor metastasis. Curr Mol Med. 2010;10:71–81. doi:CMM#07 [pii].

    Article  CAS  PubMed  Google Scholar 

  156. Naba A, et al. The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics. 2012;11:M111.014647. doi:M111.014647 [pii]10.1074/mcp.M111.014647.

    Google Scholar 

  157. Naba A, Clauser KR, Lamar JM, Carr SA, Hynes RO. Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters. Elife. 2014;3:e01308.

    Article  PubMed Central  PubMed  Google Scholar 

  158. Heino J. The collagen receptor integrins have distinct ligand recognition and signaling functions. Matrix Biol. 2000;19:319–23. doi:S0945-053X(00)00076-7 [pii].

    Article  CAS  PubMed  Google Scholar 

  159. Kern A, Eble J, Golbik R, Kuhn K. Interaction of type IV collagen with the isolated integrins alpha 1 beta 1 and alpha 2 beta 1. Eur J Biochem. 1993;215:151–9.

    Article  CAS  PubMed  Google Scholar 

  160. Fukuda K, Koshihara Y, Oda H, Ohyama M, Ooyama T. Type V collagen selectively inhibits human endothelial cell proliferation. Biochem Biophys Res Commun. 1988;151:1060–8. doi:S0006-291X(88)80473-X [pii].

    Article  CAS  PubMed  Google Scholar 

  161. Kielty CM, Whittaker SP, Grant ME, Shuttleworth CA. Attachment of human vascular smooth muscles cells to intact microfibrillar assemblies of collagen VI and fibrillin. J Cell Sci. 1992;103(Pt 2):445–51.

    CAS  PubMed  Google Scholar 

  162. Midwood KS, Schwarzbauer JE. Elastic fibers: building bridges between cells and their matrix. Curr Biol. 2002;12:R279–R81. doi:S096098220200800X..

    Article  CAS  PubMed  Google Scholar 

  163. Jovanovic J, et al. alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity. J Biol Chem. 2007;282:6743–51. doi:M607008200 [pii]10.1074/jbc.M607008200.

    Article  CAS  PubMed  Google Scholar 

  164. Timpl R, Sasaki T, Kostka G, Chu ML. Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol. 2003;4:479–89. doi:10.1038/nrm1130nrm1130 [pii].

    Article  CAS  PubMed  Google Scholar 

  165. Zou L, Cao S, Kang N, Huebert RC, Shah VH. Fibronectin induces endothelial cell migration through beta1 integrin and Src-dependent phosphorylation of fibroblast growth factor receptor-1 at tyrosines 653/654 and 766. J Biol Chem. 2012;287:7190–202. doi:M111.304972 [pii]10.1074/jbc.M111.304972.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  166. Wang J, Milner R. Fibronectin promotes brain capillary endothelial cell survival and proliferation through alpha5beta1 and alphavbeta3 integrins via MAP kinase signalling. J Neurochem. 2006;96:148–59. doi:JNC3521 [pii]10.1111/j.1471-4159.2005.03521.x.

    Article  CAS  PubMed  Google Scholar 

  167. Lawler PR, Lawler J. Molecular basis for the regulation of angiogenesis by thrombospondin-1 and—2. Cold Spring Harb Perspect Med. 2012;2:a006627. doi:10.1101/cshperspect.a006627a006627 [pii].

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  168. Chaqour B. Molecular control of vascular development by the matricellular proteins () and (). Trends Dev Biol. 2013;7:59–72.

    PubMed Central  CAS  PubMed  Google Scholar 

  169. Van Obberghen-Schilling E, et al. Fibronectin and tenascin-C: accomplices in vascular morphogenesis during development and tumor growth. Int J Dev Biol. 2011;55:511–25. doi:103243eo [pii]10.1387/ijdb.103243eo.

    Article  PubMed  CAS  Google Scholar 

  170. Williams KJ. Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis. Curr Opin Lipidol. 2001;12:477–87.

    Article  CAS  PubMed  Google Scholar 

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    Dr Iva Nikolic PhD

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Nikolic, I. (2015). More than a Scaffold: Extracellular Matrix in Vascular Signaling. In: Schmidt, M., Liebner, S. (eds) Endothelial Signaling in Development and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2907-8_7

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