The NG2 Proteoglycan in Pericyte Biology

  • William B. StallcupEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1109)


Studies of pericytes have been retarded by the lack of appropriate markers for identification of these perivascular mural cells. Use of antibodies against the NG2 proteoglycan as a pericyte marker has greatly facilitated recent studies of pericytes, emphasizing the intimate spatial relationship between pericytes and endothelial cells, allowing more accurate quantification of pericyte/endothelial cell ratios in different vascular beds, and revealing the participation of pericytes throughout all stages of blood vessel formation. The functional importance of NG2 in pericyte biology has been established via NG2 knockdown (in vitro) and knockout (in vivo) strategies that reveal significant deficits in blood vessel formation when NG2 is absent from pericytes. NG2 influences pericyte proliferation and motility by acting as an auxiliary receptor that enhances signaling through integrins and receptor tyrosine kinase growth factor receptors. By acting in a trans orientation, NG2 also activates integrin signaling in closely apposed endothelial cells, leading to enhanced maturation and formation of endothelial cell junctions. NG2 null mice exhibit reduced growth of both mammary and brain tumors that can be traced to deficits in tumor vascularization. Use of Cre-Lox technology to produce pericyte-specific NG2 null mice has revealed specific deficits in tumor vessels that include decreased pericyte ensheathment of endothelial cells, diminished assembly of the vascular basement membrane, reduced vessel patency, and increased vessel leakiness. Interestingly, myeloid-specific NG2 null mice exhibit even larger deficits in tumor vascularization, leading to correspondingly slower tumor growth. Myeloid-specific NG2 null mice are deficient in their ability to recruit macrophages to tumors and other sites of inflammation. This absence of macrophages deprives pericytes of a signal that is crucial for their ability to interact with endothelial cells. The interplay between pericytes, endothelial cells, and macrophages promises to be an extremely fertile area of future study.


NG2 proteoglycan Blood vessel development Pericytes Endothelial cells Vascular basement membrane Cell proliferation and motility Integrin signaling Growth factor receptor signaling NG2 knockdown NG2 ablation Cre-Lox technology Tumor growth Tumor vascularization Macrophage recruitment 


  1. 1.
    Dejana E, Hirschi KK, Simons M (2017) The molecular basis of endothelial cell plasticity. Nat Commun 8:14361PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Eelen G et al (2018) Endothelial cell metabolism. Physiol Rev 98(1):3–58PubMedCrossRefGoogle Scholar
  3. 3.
    Franco CA, Gerhardt H (2017) Morph or move? How distinct endothelial cell responses to blood flow shape vascular networks. Dev Cell 41(6):574–576PubMedCrossRefGoogle Scholar
  4. 4.
    Risau W (1997) Mechanisms of angiogenesis. Nature 386(6626):671–674PubMedCrossRefGoogle Scholar
  5. 5.
    Watson EC, Grant ZL, Coultas L (2017) Endothelial cell apoptosis in angiogenesis and vessel regression. Cell Mol Life Sci 74(24):4387–4403PubMedCrossRefGoogle Scholar
  6. 6.
    Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97(6):512–523PubMedCrossRefGoogle Scholar
  7. 7.
    Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314(1):15–23PubMedCrossRefGoogle Scholar
  8. 8.
    Davis GE, Senger DR (2005) Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 97(11):1093–1107PubMedCrossRefGoogle Scholar
  9. 9.
    Kalluri R (2003) Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer 3(6):422–433PubMedCrossRefGoogle Scholar
  10. 10.
    Wagenseil JE, Mecham RP (2009) Vascular extracellular matrix and arterial mechanics. Physiol Rev 89(3):957–989PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    You WK, Bonaldo P, Stallcup WB (2012) Collagen VI ablation retards brain tumor progression due to deficits in assembly of the vascular basal lamina. Am J Pathol 180(3):1145–1158PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    You WK, Stallcup WB (2015) Melanoma progression in the brain: role of pericytes, the basal lamina, and endothelial cells in tumor vascularization. In: Hayat MA (ed) Brain metastases from primary tumors, 1st edn. Academic, New York, pp 133–143CrossRefGoogle Scholar
  13. 13.
    Allt G, Lawrenson JG (2001) Pericytes: cell biology and pathology. Cells Tissues Organs 169(1):1–11PubMedCrossRefGoogle Scholar
  14. 14.
    Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology 7(4):452–464PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Betsholtz C, Lindblom P, Gerhardt H (2005) Role of pericytes in vascular morphogenesis. EXS 94:115–125Google Scholar
  16. 16.
    Sims DE (2000) Diversity within pericytes. Clin Exp Pharmacol Physiol 27(10):842–846CrossRefPubMedGoogle Scholar
  17. 17.
    Thomas H, Cowin AJ, Mills SJ (2017) The importance of pericytes in healing: wounds and other pathologies. Int J Mol Sci 18(6):1129PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Biname F (2014) Transduction of extracellular cues into cell polarity: the role of the transmembrane proteoglycan NG2. Mol Neurobiol 50(2):482–493PubMedCrossRefGoogle Scholar
  19. 19.
    Sakry D, Trotter J (2016) The role of the NG2 proteoglycan in OPC and CNS network function. Brain Res 1638(Pt B):161–166PubMedCrossRefGoogle Scholar
  20. 20.
    Stallcup WB (2002) The NG2 proteoglycan: past insights and future prospects. J Neurocytol 31(6–7):423–435PubMedCrossRefGoogle Scholar
  21. 21.
    Stallcup WB, Huang FJ (2008) A role for the NG2 proteoglycan in glioma progression. Cell Adhes Migr 2(3):192–201CrossRefGoogle Scholar
  22. 22.
    Grako KA, Stallcup WB (1995) Participation of the NG2 proteoglycan in rat aortic smooth muscle cell responses to platelet-derived growth factor. Exp Cell Res 221(1):231–240PubMedCrossRefGoogle Scholar
  23. 23.
    Schrappe M et al (1991) Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells. Cancer Res 51(18):4986–4993PubMedGoogle Scholar
  24. 24.
    Beck L Jr, D’Amore PA (1997) Vascular development: cellular and molecular regulation. FASEB J 11(5):365–373PubMedCrossRefGoogle Scholar
  25. 25.
    Hirschi KK et al (1999) Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res 84(3):298–305PubMedCrossRefGoogle Scholar
  26. 26.
    Orlidge A, D'Amore PA (1987) Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J Cell Biol 105(3):1455–1462PubMedCrossRefGoogle Scholar
  27. 27.
    Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol 109(1):309–315PubMedCrossRefGoogle Scholar
  28. 28.
    Nayak RC et al (1988) A monoclonal antibody (3G5)-defined ganglioside antigen is expressed on the cell surface of microvascular pericytes. J Exp Med 167(3):1003–1015PubMedCrossRefGoogle Scholar
  29. 29.
    Schlingemann RO et al (1996) Aminopeptidase a is a constituent of activated pericytes in angiogenesis. J Pathol 179(4):436–442PubMedCrossRefGoogle Scholar
  30. 30.
    Lindahl P, Betsholtz C (1998) Not all myofibroblasts are alike: revisiting the role of PDGF-A and PDGF-B using PDGF-targeted mice. Curr Opin Nephrol Hypertens 7(1):21–26PubMedCrossRefGoogle Scholar
  31. 31.
    Lindahl P et al (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277(5323):242–245PubMedCrossRefGoogle Scholar
  32. 32.
    Song S et al (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7(9):870–9PubMedCrossRefGoogle Scholar
  33. 33.
    Ozerdem U et al (2001) NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn 222(2):218–227PubMedCrossRefGoogle Scholar
  34. 34.
    Ozerdem U, Monosov E, Stallcup WB (2002) NG2 proteoglycan expression by pericytes in pathological microvasculature. Microvasc Res 63(1):129–134PubMedCrossRefGoogle Scholar
  35. 35.
    Ozerdem U, Stallcup WB (2003) Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis 6(3):241–249PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Tigges U et al (2008) FGF2-dependent neovascularization of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages. Development 135(3):523–532PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Virgintino D et al (2007) An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis. Angiogenesis 10(1):35–45PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hellstrom M et al (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126(14):3047–3055PubMedPubMedCentralGoogle Scholar
  39. 39.
    Gibby K et al (2012) Early vascular deficits are correlated with delayed mammary tumorigenesis in the MMTV-PyMT transgenic mouse following genetic ablation of the neuron-glial antigen 2 proteoglycan. Breast Cancer Res 14(2):R67PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Huang FJ et al (2010) Pericyte deficiencies lead to aberrant tumor vascularization in the brain of the NG2 null mouse. Dev Biol 344(2):1035–1046PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    You WK et al (2014) NG2 proteoglycan promotes tumor vascularization via integrin-dependent effects on pericyte function. Angiogenesis 17(1):61–76PubMedCrossRefGoogle Scholar
  42. 42.
    Fukushi J et al (2003) Expression of NG2 proteoglycan during endochondral and intramembranous ossification. Dev Dyn 228(1):143–148PubMedCrossRefGoogle Scholar
  43. 43.
    Kadoya K et al (2008) NG2 proteoglycan expression in mouse skin: altered postnatal skin development in the NG2 null mouse. J Histochem Cytochem 56(3):295–303PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Kucharova K, Stallcup WB (2017) Distinct NG2 proteoglycan-dependent roles of resident microglia and bone marrow-derived macrophages during myelin damage and repair. PLoS One 12(11):e0187530PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Nishiyama A et al (1996) Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain. J Neurosci Res 43(3):299–314PubMedCrossRefGoogle Scholar
  46. 46.
    Yotsumoto F et al (2015) NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte-endothelial cell interactions required for brain tumor vascularization. Oncoimmunology 4(4):e1001204PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Kucharova K, Stallcup WB (2015) NG2-proteoglycan-dependent contributions of oligodendrocyte progenitors and myeloid cells to myelin damage and repair. J Neuroinflammation 12(1):161PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Brachvogel B et al (2005) Perivascular cells expressing annexin A5 define a novel mesenchymal stem cell-like population with the capacity to differentiate into multiple mesenchymal lineages. Development 132(11):2657–2668PubMedCrossRefGoogle Scholar
  49. 49.
    Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3(3):229–230PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Crisan M et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Traktuev DO et al (2008) A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res 102(1):77–85PubMedCrossRefGoogle Scholar
  52. 52.
    She ZG et al (2016) NG2 proteoglycan ablation reduces foam cell formation and atherogenesis via decreased low-density lipoprotein retention by synthetic smooth muscle cells. Arterioscler Thromb Vasc Biol 36(1):49–59PubMedCrossRefGoogle Scholar
  53. 53.
    Tigges U, Komatsu M, Stallcup WB (2013) Adventitial pericyte progenitor/mesenchymal stem cells participate in the restenotic response to arterial injury. J Vasc Res 50(2):134–144PubMedCrossRefGoogle Scholar
  54. 54.
    Murfee WL, Skalak TC, Peirce SM (2005) Differential arterial/venous expression of NG2 proteoglycan in perivascular cells along microvessels: identifying a venule-specific phenotype. Microcirculation 12(2):151–160PubMedCrossRefGoogle Scholar
  55. 55.
    Murfee WL et al (2006) Perivascular cells along venules upregulate NG2 expression during microvascular remodeling. Microcirculation 13(3):261–273PubMedCrossRefGoogle Scholar
  56. 56.
    Fang X et al (1999) Cytoskeletal reorganization induced by engagement of the NG2 proteoglycan leads to cell spreading and migration. Mol Biol Cell 10(10):3373–3387PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Lin XH, Dahlin-Huppe K, Stallcup WB (1996) Interaction of the NG2 proteoglycan with the actin cytoskeleton. J Cell Biochem 63(4):463–477PubMedCrossRefGoogle Scholar
  58. 58.
    Lin XH et al (1996) NG2 proteoglycan and the actin-binding protein fascin define separate populations of actin-containing filopodia and lamellipodia during cell spreading and migration. Mol Biol Cell 7(12):1977–1993PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Majumdar M, Vuori K, Stallcup WB (2003) Engagement of the NG2 proteoglycan triggers cell spreading via rac and p130cas. Cell Signal 15(1):79–84PubMedCrossRefGoogle Scholar
  60. 60.
    Couchman JR (2003) Syndecans: proteoglycan regulators of cell-surface microdomains? Nat Rev Mol Cell Biol 4(12):926–937PubMedCrossRefGoogle Scholar
  61. 61.
    Cattaruzza S et al (2013) Multivalent proteoglycan modulation of FGF mitogenic responses in perivascular cells. Angiogenesis 16(2):309–327PubMedCrossRefGoogle Scholar
  62. 62.
    Goretzki L et al (1999) High-affinity binding of basic fibroblast growth factor and platelet-derived growth factor-AA to the core protein of the NG2 proteoglycan. J Biol Chem 274(24):16831–16837PubMedCrossRefGoogle Scholar
  63. 63.
    Rapraeger AC (1995) In the clutches of proteoglycans: how does heparan sulfate regulate FGF binding? Chem Biol 2(10):645–649PubMedCrossRefGoogle Scholar
  64. 64.
    Grako KA et al (1999) PDGF (alpha)-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse. J Cell Sci 112(Pt 6):905–915PubMedGoogle Scholar
  65. 65.
    Nishiyama A et al (1996) Interaction between NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells is required for optimal response to PDGF. J Neurosci Res 43(3):315–330PubMedCrossRefGoogle Scholar
  66. 66.
    Chekenya M et al (2008) The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene 27(39):5182–5194PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Fukushi J, Makagiansar IT, Stallcup WB (2004) NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell 15(8):3580–3590PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Stallcup WB (2017) NG2 proteoglycan enhances brain tumor progression by promoting beta-1 integrin activation in both cis and trans orientations. Cancers (Basel) 9(4) E31Google Scholar
  69. 69.
    Makagiansar IT et al (2004) Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates polarized membrane distribution and cell motility. J Biol Chem 279(53):55262–55270PubMedCrossRefGoogle Scholar
  70. 70.
    Makagiansar IT et al (2007) Differential phosphorylation of NG2 proteoglycan by ERK and PKCalpha helps balance cell proliferation and migration. J Cell Biol 178(1):155–165PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Barritt DS et al (2000) The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2. J Cell Biochem 79(2):213–224PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Chatterjee N et al (2008) Interaction of syntenin-1 and the NG2 proteoglycan in migratory oligodendrocyte precursor cells. J Biol Chem 283(13):8310–8317PubMedCrossRefGoogle Scholar
  73. 73.
    Stegmuller J et al (2003) The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. Implications for glial-neuronal signaling. J Biol Chem 278(6):3590–3598PubMedCrossRefGoogle Scholar
  74. 74.
    Ozerdem U, Stallcup WB (2004) Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan. Angiogenesis 7(3):269–276PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Luque A et al (1996) Activated conformations of very late activation integrins detected by a group of antibodies (HUTS) specific for a novel regulatory region (355–425) of the common beta 1 chain. J Biol Chem 271(19):11067–11075PubMedCrossRefGoogle Scholar
  76. 76.
    Tillet E et al (1997) The membrane-spanning proteoglycan NG2 binds to collagens V and VI through the central nonglobular domain of its core protein. J Biol Chem 272(16):10769–10776PubMedCrossRefGoogle Scholar
  77. 77.
    Lenter M et al (1993) A monoclonal antibody against an activation epitope on mouse integrin chain beta 1 blocks adhesion of lymphocytes to the endothelial integrin alpha 6 beta 1. Proc Natl Acad Sci U S A 90(19):9051–9055PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Lin EY et al (2003) Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol 163(5):2113–2126PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Maglione JE et al (2001) Transgenic Polyoma middle-T mice model premalignant mammary disease. Cancer Res 61(22):8298–8305PubMedGoogle Scholar
  80. 80.
    Fidler IJ (1973) Selection of successive tumour lines for metastasis. Nat New Biol 242(118):148–149PubMedCrossRefGoogle Scholar
  81. 81.
    Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410PubMedCrossRefGoogle Scholar
  82. 82.
    Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3):353–364PubMedCrossRefGoogle Scholar
  83. 83.
    Folkman J et al (1989) Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339(6219):58–61PubMedCrossRefGoogle Scholar
  84. 84.
    Brekke C et al (2006) NG2 expression regulates vascular morphology and function in human brain tumours. NeuroImage 29(3):965–976PubMedCrossRefGoogle Scholar
  85. 85.
    Maciag PC et al (2008) Cancer immunotherapy targeting the high molecular weight melanoma-associated antigen protein results in a broad antitumor response and reduction of pericytes in the tumor vasculature. Cancer Res 68(19):8066–8075PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Wang J et al (2011) Targeting the NG2/CSPG4 proteoglycan retards tumour growth and angiogenesis in preclinical models of GBM and melanoma. PLoS One 6(7):e23062PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Coffelt SB, Hughes R, Lewis CE (2009) Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochim Biophys Acta 1796(1):11–18PubMedGoogle Scholar
  88. 88.
    De Palma M, Naldini L (2009) Tie2-expressing monocytes (TEMs): novel targets and vehicles of anticancer therapy? Biochim Biophys Acta 1796(1):5–10PubMedGoogle Scholar
  89. 89.
    Lin EY et al (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66(23):11238–11246PubMedCrossRefGoogle Scholar
  90. 90.
    Noy R, Pollard JW (2014) Tumor-associated macrophages: from mechanisms to therapy. Immunity 41(1):49–61PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Chang Y et al (2012) Ablation of NG2 proteoglycan leads to deficits in brown fat function and to adult onset obesity. PLoS One 7(1):e30637PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Foo SS et al (2006) Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly. Cell 124(1):161–173PubMedCrossRefGoogle Scholar
  93. 93.
    Stockmann C et al (2008) Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature 456(7223):814–818PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Luo Y, Radice GL (2005) N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis. J Cell Biol 169(1):29–34PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Gerhardt H, Wolburg H, Redies C (2000) N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken. Dev Dyn 218(3):472–479PubMedCrossRefGoogle Scholar
  96. 96.
    Gaengel K et al (2009) Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 29(5):630–638CrossRefPubMedGoogle Scholar
  97. 97.
    Bergers G et al (2003) Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 111(9):1287–1295PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Saharinen P, Alitalo K (2003) Double target for tumor mass destruction. J Clin Invest 111(9):1277–1280PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Lu C et al (2007) Dual targeting of endothelial cells and pericytes in antivascular therapy for ovarian carcinoma. Clin Cancer Res 13(14):4209–4217PubMedCrossRefGoogle Scholar
  100. 100.
    Brand C et al (2016) NG2 proteoglycan as a pericyte target for anticancer therapy by tumor vessel infarction with retargeted tissue factor. Oncotarget 7(6):6774–6789PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Burg MA et al (1999) NG2 proteoglycan-binding peptides target tumor neovasculature. Cancer Res 59(12):2869–2874PubMedGoogle Scholar
  102. 102.
    Mills SJ, Cowin AJ, Kaur P (2013) Pericytes, mesenchymal stem cells and the wound healing process. Cell 2(3):621–634CrossRefGoogle Scholar
  103. 103.
    Sa da Bandeira D, Casamitjana J, Crisan M (2017) Pericytes, integral components of adult hematopoietic stem cell niches. Pharmacol Ther 171:104–113PubMedCrossRefGoogle Scholar
  104. 104.
    De Palma M et al (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8(3):211–226PubMedCrossRefGoogle Scholar
  105. 105.
    Guillemin GJ, Brew BJ (2004) Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol 75(3):388–397PubMedCrossRefGoogle Scholar
  106. 106.
    Coffelt SB et al (2010) Elusive identities and overlapping phenotypes of proangiogenic myeloid cells in tumors. Am J Pathol 176(4):1564–1576PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Tumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery InstituteLa JollaUSA

Personalised recommendations