Advertisement

Glioblastoma Stem Cells and Their Microenvironment

  • Anirudh Sattiraju
  • Kiran Kumar Solingapuram Sai
  • Akiva MintzEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1041)

Abstract

Glioblastoma (GBM) is the most common primary malignant astrocytoma associated with a poor patient survival. Apart from arising de novo, GBMs also occur due to progression of slower growing grade III astrocytomas. GBM is characterized by extensive hypoxia, angiogenesis, proliferation and invasion. Standard treatment options such as surgical resection, radiation therapy and chemotherapy have increased median patient survival to 14.6 months in adults but recurrent disease arising from treatment resistant cancer cells often results in patient mortality. These treatment resistant cancer cells have been found to exhibit stem cell like properties. Strategies to identify or target these Glioblastoma Stem Cells (GSC) have proven to be unsuccessful so far. Studies on cancer stem cells (CSC) within GBM and other cancers have highlighted the importance of paracrine signaling networks within their microenvironment on the growth and maintenance of CSCs. The study of GSCs and their communication with various cell populations within their microenvironment is therefore not only important to understand the biology of GBMs but also to predict response to therapies and to identify novel targets which could stymy support to treatment resistant cancer cells and prevent disease recurrence. The purpose of this chapter is to introduce the concept of GSCs and to detail the latest findings indicating the role of various cellular subtypes within their microenvironment on their survival, proliferation and differentiation.

Keywords

GBM Glioblastoma stem cells Microenvironment Cancer stem cells 

References

  1. Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200(6):629–638PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ (2010) Structure and function of the blood–brain barrier. Neurobiol Dis 37(1):13–25PubMedCrossRefGoogle Scholar
  3. Agarwal S, Manchanda P, Vogelbaum MA, Ohlfest JR, Elmquist WF (2013) Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells: findings in an orthotopic rat xenograft model of glioma. Drug Metab Dispos 41(1):33–39PubMedPubMedCentralCrossRefGoogle Scholar
  4. Ahmed AU, Auffinger B, Lesniak MS (2013) Understanding glioma stem cells: rationale, clinical relevance and therapeutic strategies. Expert Rev Neurother 13(5):545–555PubMedPubMedCentralCrossRefGoogle Scholar
  5. Alcantara Llaguno SR, Wang Z, Sun D et al (2015) Adult lineage restricted CNS progenitors specify distinct glioblastoma subtypes. Cancer Cell 28(4):429–440PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bao S, Wu Q, McLendon RE et al (2006a) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760PubMedCrossRefGoogle Scholar
  7. Bao S, Wu Q, Sathornsumetee S et al (2006b) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66(16):7843–7848PubMedCrossRefGoogle Scholar
  8. Bar EE, Lin A, Mahairaki V, Matsui W, Eberhart CG (2010) Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres. Am J Pathol 177(3):1491–1502PubMedPubMedCentralCrossRefGoogle Scholar
  9. Baskar R, Lee KA, Yeo R, Yeoh K-W (2012) Cancer and radiation therapy: current advances and future directions. Int J Med Sci 9(3):193–199PubMedPubMedCentralCrossRefGoogle Scholar
  10. Birbrair A, Sattiraju A, Zhu D et al (2016) Novel peripherally derived neural-like stem cells as therapeutic carriers for treating glioblastomas. Stem Cells Transl Med 14:2016Google Scholar
  11. Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1(1):46–54PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bleau AM, Hambardzumyan D, Ozawa T et al (2009) PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 4(3):226–235PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bonavia R, Inda M-d-M, Cavenee WK, Furnari FB (2011) Heterogeneity maintenance in glioblastoma: a social network. Cancer Res 71(12):4055–4060PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bradshaw A, Wickremsekera A, Tan ST, Peng L, Davis PF, Itinteang T (2016) Cancer stem cell hierarchy in glioblastoma multiforme. Front Surg 3:21PubMedPubMedCentralGoogle Scholar
  15. Brat DJ, Castellano-Sanchez AA, Hunter SB et al (2004) Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population. Cancer Res 64(3):920–927PubMedCrossRefGoogle Scholar
  16. Brooks MD, Sengupta R, Snyder SC, Rubin JB (2013) Hitting them where they live: targeting the glioblastoma perivascular stem cell niche. Curr Pathobiol Rep 1(2):101–110PubMedPubMedCentralCrossRefGoogle Scholar
  17. Burgess A, Nhan T, Moffatt C, Klibanov AL, Hynynen K (2014) Analysis of focused ultrasound-induced blood-brain barrier permeability in a mouse model of Alzheimer’s disease using two-photon microscopy. J Control Release 192:243–248PubMedCrossRefGoogle Scholar
  18. Cabrera MC, Hollingsworth RE, Hurt EM (2015) Cancer stem cell plasticity and tumor hierarchy. World J Stem Cells 7(1):27–36PubMedPubMedCentralCrossRefGoogle Scholar
  19. Calabrese C, Poppleton H, Kocak M et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11(1):69–82PubMedCrossRefGoogle Scholar
  20. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407(6801):249–257PubMedCrossRefGoogle Scholar
  21. Chaichana KL (2014) The need to continually redefine the goals of surgery for glioblastoma. Neurooncology 30:2014Google Scholar
  22. Charles N, Ozawa T, Squatrito M et al (2010) Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell 6(2):141–152PubMedCrossRefGoogle Scholar
  23. Chen J, Ding Z, Peng Y et al (2014) HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-glycoprotein. PLoS One 9(6):e98882PubMedPubMedCentralCrossRefGoogle Scholar
  24. Cheng L, Huang Z, Zhou W et al (2013) Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell 153(1):139–152PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cho DY, Lin SZ, Yang WK et al (2013) Targeting cancer stem cells for treatment of glioblastoma multiforme. Cell Transplant 22(4):731–739PubMedCrossRefGoogle Scholar
  26. Chou C-W, Wang C-C, Wu C-P et al (2012) Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1. Neurooncology 14(10):1227–1238Google Scholar
  27. Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284PubMedCrossRefGoogle Scholar
  28. De Palma M, Murdoch C, Venneri MA, Naldini L, Lewis CE (2007) Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol 28(12):519–524PubMedCrossRefGoogle Scholar
  29. Dewhirst MW, Cao Y, Moeller B (2008) Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8(6):425–437PubMedPubMedCentralCrossRefGoogle Scholar
  30. Dick JE (2009) Looking ahead in cancer stem cell research. Nat Biotechnol 27(1):44–46PubMedCrossRefGoogle Scholar
  31. Doetsch F (2003) A niche for adult neural stem cells. Curr Opin Genet Dev 13(5):543–550PubMedCrossRefGoogle Scholar
  32. Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK (2011) CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clin Cancer Res 17(8):2074–2080PubMedPubMedCentralCrossRefGoogle Scholar
  33. El Hallani S, Boisselier B, Peglion F et al (2010) A new alternative mechanism in glioblastoma vascularization: tubular vasculogenic mimicry. Brain 133(Pt 4):973–982PubMedPubMedCentralCrossRefGoogle Scholar
  34. Eriksson PS, Perfilieva E, Bjork-Eriksson T et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317PubMedCrossRefGoogle Scholar
  35. Evans SM, Judy KD, Dunphy I et al (2004) Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding. Cancer Res 64(5):1886–1892PubMedCrossRefGoogle Scholar
  36. Eyupoglu IY, Buchfelder M, Savaskan NE (2013) Surgical resection of malignant gliomas—role in optimizing patient outcome. Nat Rev Neurol 9(3):141–151PubMedCrossRefGoogle Scholar
  37. Fan X, Khaki L, Zhu TS et al (2010) NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28(1):5–16PubMedPubMedCentralGoogle Scholar
  38. Fang D, Nguyen TK, Leishear K et al (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65(20):9328–9337PubMedCrossRefGoogle Scholar
  39. Fang DD, Kim YJ, Lee CN et al (2010) Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery. Br J Cancer 102(8):1265–1275PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fidoamore A, Cristiano L, Antonosante A et al (2016) Glioblastoma stem cells microenvironment: the paracrine roles of the niche in drug and radioresistance. Stem Cells Int 2016:6809105PubMedPubMedCentralCrossRefGoogle Scholar
  41. Folkins C, Shaked Y, Man S et al (2009) Glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal-derived factor 1. Cancer Res 69(18):7243–7251PubMedPubMedCentralCrossRefGoogle Scholar
  42. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267(16):10931–10934PubMedGoogle Scholar
  43. Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I (1988) A heparin-binding angiogenic protein—basic fibroblast growth factor—is stored within basement membrane. Am J Pathol 130(2):393–400PubMedPubMedCentralGoogle Scholar
  44. Fortunel NO, Otu HH, Ng HH et al (2003) Comment on “ ‘Stemness’: transcriptional profiling of embryonic and adult stem cells” and “a stem cell molecular signature”. Science 302(5644):393. author reply 393PubMedCrossRefGoogle Scholar
  45. Friedmann-Morvinski D, Verma IM (2014) Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep 15(3):244–253PubMedPubMedCentralCrossRefGoogle Scholar
  46. Gage FH (2000) Mammalian neural stem cells. Science 287(5457):1433–1438PubMedCrossRefGoogle Scholar
  47. Garcion E, Halilagic A, Faissner A, French-Constant C (2004) Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development 131(14):3423–3432PubMedCrossRefGoogle Scholar
  48. Gerstner E, Zhang Z, Fink J et al (2016) ACRIN 6684: assessment of tumor hypoxia in newly diagnosed GBM using 18F-FMISO PET and MRI. Clin Cancer Res 22:5079–5086PubMedPubMedCentralCrossRefGoogle Scholar
  49. Gilbertson RJ, Rich JN (2007) Making a tumour's bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer 7(10):733–736PubMedCrossRefGoogle Scholar
  50. Gilmore AP, Romer LH (1996) Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation. Mol Biol Cell 7(8):1209–1224PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gorlach A, Bonello S (2008) The cross-talk between NF-kappaB and HIF-1: further evidence for a significant liaison. Biochem J 412(3):e17–e19PubMedCrossRefGoogle Scholar
  52. Greene-Schloesser D, Robbins ME (2012) Radiation-induced cognitive impairment-from bench to bedside. Neurooncology 14(suppl 4):iv37–iv44Google Scholar
  53. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD (2012) Radiation-induced brain injury: a review. Front Oncol 2:73PubMedPubMedCentralCrossRefGoogle Scholar
  54. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674Google Scholar
  55. Hardee ME, Zagzag D (2012) Mechanisms of glioma-associated neovascularization. Am J Pathol 181(4):1126–1141PubMedPubMedCentralCrossRefGoogle Scholar
  56. Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57(2):173–185PubMedCrossRefGoogle Scholar
  57. Heddleston JM, Li Z, Hjelmeland AB, Rich JN (2009) The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 8(20):3274–3284PubMedPubMedCentralCrossRefGoogle Scholar
  58. Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN (2010) Hypoxia inducible factors in cancer stem cells. Br J Cancer 102(5):789–795PubMedPubMedCentralCrossRefGoogle Scholar
  59. Heddleston JM, Hitomi M, Venere M et al (2011) Glioma stem cell maintenance: the role of the microenvironment. Curr Pharm Des 17(23):2386–2401PubMedPubMedCentralCrossRefGoogle Scholar
  60. Holash J, Maisonpierre PC, Compton D et al (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284(5422):1994–1998PubMedCrossRefGoogle Scholar
  61. Hottinger AF, Stupp R, Homicsko K (2014) Standards of care and novel approaches in the management of glioblastoma multiforme. Chin J Cancer 33(1):32–39PubMedPubMedCentralCrossRefGoogle Scholar
  62. Huang P, Rani MR, Ahluwalia MS et al (2012) Endothelial expression of TNF receptor-1 generates a proapoptotic signal inhibited by integrin alpha6beta1 in glioblastoma. Cancer Res 72(6):1428–1437PubMedPubMedCentralCrossRefGoogle Scholar
  63. Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA (2002) Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39(3):193–206PubMedCrossRefGoogle Scholar
  64. Jackson M, Hassiotou F, Nowak A (2015) Glioblastoma stem-like cells: at the root of tumor recurrence and a therapeutic target. Carcinogenesis 36(2):177–185PubMedCrossRefGoogle Scholar
  65. Jhaveri N, Chen TC, Hofman FM (2016) Tumor vasculature and glioma stem cells: contributions to glioma progression. Cancer Lett 380(2):545–551PubMedCrossRefGoogle Scholar
  66. Jordao JF, Thevenot E, Markham-Coultes K et al (2013) Amyloid-beta plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound. Exp Neurol 248:16–29PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kang TW, Choi SW, Yang SR et al (2014) Growth arrest and forced differentiation of human primary glioblastoma multiformE by a novel small molecule. Sci Rep 4:5546PubMedPubMedCentralCrossRefGoogle Scholar
  68. Kelly JJ, Stechishin O, Chojnacki A et al (2009) Proliferation of human glioblastoma stem cells occurs independently of exogenous mitogens. Stem Cells 27(8):1722–1733PubMedCrossRefGoogle Scholar
  69. Konofagou EE, Tung YS, Choi J, Deffieux T, Baseri B, Vlachos F (2012) Ultrasound-induced blood-brain barrier opening. Curr Pharm Biotechnol 13(7):1332–1345PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kreso A, Dick John E (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14(3):275–291PubMedCrossRefGoogle Scholar
  71. Laks DR, Masterman-Smith M, Visnyei K et al (2009) Neurosphere formation is an independent predictor of clinical outcome in malignant glioma. Stem Cells 27(4):980–987PubMedPubMedCentralCrossRefGoogle Scholar
  72. Lapidot T, Sirard C, Vormoor J et al (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648PubMedCrossRefGoogle Scholar
  73. Lathia JD, Gallagher J, Heddleston JM et al (2010) Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell 6(5):421–432PubMedPubMedCentralCrossRefGoogle Scholar
  74. Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CLL, Rich JN (2015) Cancer stem cells in glioblastoma. Genes Dev 29(12):1203–1217PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lee G, Hall RR, Ahmed AU (2016) Cancer stem cells: cellular plasticity, niche, and its clinical relevance. J Stem Cell Res Ther 6(10):363PubMedPubMedCentralCrossRefGoogle Scholar
  76. Leins A, Riva P, Lindstedt R, Davidoff MS, Mehraein P, Weis S (2003) Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Cancer 98(11):2430–2439PubMedCrossRefGoogle Scholar
  77. Leventhal C, Rafii S, Rafii D, Shahar A, Goldman SA (1999) Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma. Mol Cell Neurosci 13(6):450–464PubMedCrossRefGoogle Scholar
  78. Li Z, Bao S, Wu Q et al (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15(6):501–513PubMedPubMedCentralCrossRefGoogle Scholar
  79. Liebelt BD, Shingu T, Zhou X, Ren J, Shin SA, Hu J (2016) Glioma stem cells: signaling, microenvironment, and therapy. Stem Cells Int 2016:7849890PubMedPubMedCentralCrossRefGoogle Scholar
  80. Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedPubMedCentralCrossRefGoogle Scholar
  81. Louvi A, Artavanis-Tsakonas S (2006) Notch signalling in vertebrate neural development. Nat Rev Neurosci 7(2):93–102PubMedCrossRefGoogle Scholar
  82. Mannino M, Chalmers AJ (2011) Radioresistance of glioma stem cells: Intrinsic characteristic or property of the ‘microenvironment-stem cell unit’? Mol Oncol 5(4):374–386PubMedPubMedCentralCrossRefGoogle Scholar
  83. Mao XG, Xue XY, Wang L et al (2013) CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia. Neurooncology 15(7):865–879Google Scholar
  84. Mathieu J, Zhou W, Xing Y et al (2014) Hypoxia inducible factors have distinct and stage-specific roles during reprogramming of human cells to pluripotency. Cell Stem Cell 14(5):592–605PubMedPubMedCentralCrossRefGoogle Scholar
  85. McCord AM, Jamal M, Shankavaram UT, Lang FF, Camphausen K, Tofilon PJ (2009) Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro. Mol Cancer Res 7(4):489–497PubMedCrossRefGoogle Scholar
  86. MDM I, Bonavia R, Mukasa A et al (2010) Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev 24(16):1731–1745CrossRefGoogle Scholar
  87. Mendez O, Zavadil J, Esencay M et al (2010) Knock down of HIF-1alpha in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres. Mol Cancer 9:133PubMedPubMedCentralCrossRefGoogle Scholar
  88. Merkle FT, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci U S A 101(50):17528–17532PubMedPubMedCentralCrossRefGoogle Scholar
  89. Murat A, Migliavacca E, Gorlia T et al (2008a) Stem cell–related “Self-Renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26(18):3015–3024PubMedCrossRefGoogle Scholar
  90. Murat A, Migliavacca E, Gorlia T et al (2008b) Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26(18):3015–3024PubMedCrossRefGoogle Scholar
  91. Nakada M, Nambu E, Furuyama N et al (2013) Integrin [alpha]3 is overexpressed in glioma stem-like cells and promotes invasion. Br J Cancer 108(12):2516–2524PubMedPubMedCentralCrossRefGoogle Scholar
  92. Nath B, Szabo G (2012) Hypoxia and hypoxia inducible factors: diverse roles in liver diseases. Hepatology 55(2):622–633PubMedPubMedCentralCrossRefGoogle Scholar
  93. Nguyen LV, Vanner R, Dirks P, Eaves CJ (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12(2):133–143PubMedGoogle Scholar
  94. Nhan T, Burgess A, Lilge L, Hynynen K (2014) Modeling localized delivery of Doxorubicin to the brain following focused ultrasound enhanced blood-brain barrier permeability. Phys Med Biol 59(20):5987–6004PubMedCrossRefGoogle Scholar
  95. Nishide K, Nakatani Y, Kiyonari H, Kondo T (2009) Glioblastoma formation from cell population depleted of Prominin1-expressing cells. PLoS One 4(8):e6869PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ogden AT, Waziri AE, Lochhead RA et al (2008) Identification of A2B5+CD133- tumor-initiating cells in adult human gliomas. Neurosurgery 62(2):505–514. discussion 514-505PubMedCrossRefGoogle Scholar
  97. Paez-Gonzalez P, Asrican B, Rodriguez E, Kuo CT (2014) Identification of distinct ChAT+ neurons and activity-dependent control of postnatal SVZ neurogenesis. Nat Neurosci 17(7):934–942PubMedPubMedCentralCrossRefGoogle Scholar
  98. Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425(4):479–494PubMedCrossRefGoogle Scholar
  99. Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2(1):3–14PubMedPubMedCentralCrossRefGoogle Scholar
  100. Patel AP, Tirosh I, Trombetta JJ et al (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344(6190):1396–1401PubMedPubMedCentralCrossRefGoogle Scholar
  101. Persano L, Pistollato F, Rampazzo E et al (2012) BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1[alpha] stability and MGMT expression. Cell Death Dis e412:3Google Scholar
  102. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood–brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1(3):223–236PubMedCrossRefGoogle Scholar
  103. Pistollato F, Chen H-L, Rood BR et al (2009) Hypoxia and HIF1α repress the differentiative effects of BMPs in high-grade glioma. Stem Cells 27(1):7–17PubMedCrossRefGoogle Scholar
  104. Pistollato F, Abbadi S, Rampazzo E et al (2010) Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells 28(5):851–862PubMedGoogle Scholar
  105. Ramirez-Castillejo C, Sanchez-Sanchez F, Andreu-Agullo C et al (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9(3):331–339PubMedCrossRefGoogle Scholar
  106. Reiss Y, Machein MR, Plate KH (2005) The role of angiopoietins during angiogenesis in gliomas. Brain Pathol 15(4):311–317PubMedCrossRefGoogle Scholar
  107. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111PubMedCrossRefGoogle Scholar
  108. Ricci-Vitiani L, Pallini R, Biffoni M et al (2010) Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468(7325):824–828PubMedCrossRefGoogle Scholar
  109. Riquelme PA, Drapeau E, Doetsch F (2008) Brain micro-ecologies: neural stem cell niches in the adult mammalian brain. Philos Trans R Soc Lond Ser B Biol Sci 363(1489):123–137CrossRefGoogle Scholar
  110. Rong Y, Durden DL, Van Meir EG, Brat DJ (2006) ‘Pseudopalisading’ necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis. J Neuropathol Exp Neurol 65(6):529PubMedCrossRefGoogle Scholar
  111. Safa AR, Saadatzadeh MR, Cohen-Gadol AA, Pollok KE, Bijangi-Vishehsaraei K (2015) Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs. Genes Diseases 2(2):152–163PubMedPubMedCentralCrossRefGoogle Scholar
  112. Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441(7097):1075–1079PubMedCrossRefGoogle Scholar
  113. Scheres B (2007) Stem-cell niches: nursery rhymes across kingdoms. Nat Rev Mol Cell Biol 8(5):345–354PubMedCrossRefGoogle Scholar
  114. Seidel S, Garvalov BK, Wirta V et al (2010) A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain 133(Pt 4):983–995PubMedCrossRefGoogle Scholar
  115. Semenza GL (2010) Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29(5):625–634PubMedCrossRefGoogle Scholar
  116. Semenza GL (2013) HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 123(9):3664–3671PubMedPubMedCentralCrossRefGoogle Scholar
  117. Shackleton M, Quintana E, Fearon ER, Morrison SJ (2009) Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 138(5):822–829PubMedCrossRefGoogle Scholar
  118. Singh SK, Clarke ID, Terasaki M et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMedGoogle Scholar
  119. Singh SK, Hawkins C, Clarke ID et al (2004a) Identification of human brain tumour initiating cells. Nature 432Google Scholar
  120. Singh SK, Clarke ID, Hide T, Dirks PB (2004b) Cancer stem cells in nervous system tumors. Oncogene 23(43):7267–7273PubMedCrossRefGoogle Scholar
  121. Soda Y, Marumoto T, Friedmann-Morvinski D et al (2011) Transdifferentiation of glioblastoma cells into vascular endothelial cells. Proc Natl Acad Sci U S A 108(11):4274–4280PubMedPubMedCentralCrossRefGoogle Scholar
  122. Son MJ, Woolard K, Nam DH, Lee J, Fine HA (2009) SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell 4(5):440–452PubMedCrossRefGoogle Scholar
  123. Sottoriva A, Spiteri I, Piccirillo SGM et al (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci 110(10):4009–4014PubMedPubMedCentralCrossRefGoogle Scholar
  124. Stier S, Ko Y, Forkert R et al (2005) Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J Exp Med 201(11):1781–1791PubMedPubMedCentralCrossRefGoogle Scholar
  125. Stockhausen M-T, Kristoffersen K, Poulsen HS (2009) The functional role of Notch signaling in human gliomas. Neurooncology 12(2):199–211Google Scholar
  126. Sun X, Cheng G, Hao M et al (2010) CXCL12/CXCR4/CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev 29(4):709–722PubMedPubMedCentralCrossRefGoogle Scholar
  127. Tallet AV, Azria D, Barlesi F et al (2012) Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol 7(1):77PubMedPubMedCentralCrossRefGoogle Scholar
  128. Tan BT, Park CY, Ailles LE, Weissman IL (2006) The cancer stem cell hypothesis: a work in progress. Lab Investig 86(12):1203–1207PubMedCrossRefGoogle Scholar
  129. Tavazoie M, Van der Veken L, Silva-Vargas V et al (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3(3):279–288PubMedCrossRefGoogle Scholar
  130. Tomuleasa C, Soritau O, Rus-Ciuca D et al (2010) Isolation and characterization of hepatic cancer cells with stem-like properties from hepatocellular carcinoma. J Gastrointestin Liver Dis 19(1):61–67PubMedGoogle Scholar
  131. Uchida N, Buck DW, He D et al (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci 97(26):14720–14725PubMedPubMedCentralCrossRefGoogle Scholar
  132. Uhm JH, Dooley NP, Kyritsis AP, Rao JS, Gladson CL (1999) Vitronectin, a glioma-derived extracellular matrix protein, protects tumor cells from apoptotic death. Clin Cancer Res 5(6):1587–1594PubMedGoogle Scholar
  133. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60(3):166–193PubMedPubMedCentralCrossRefGoogle Scholar
  134. Venneri MA, De Palma M, Ponzoni M et al (2007) Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 109(12):5276–5285PubMedCrossRefGoogle Scholar
  135. Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110PubMedPubMedCentralCrossRefGoogle Scholar
  136. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6(6):425–436PubMedCrossRefGoogle Scholar
  137. Wang CY, Mayo MW, Baldwin AS Jr (1996) TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science 274(5288):784–787PubMedCrossRefGoogle Scholar
  138. Wang J, Wakeman TP, Latha JD et al (2010a) Notch promotes radioresistance of glioma stem cells. Stem Cells 28(1):17–28PubMedPubMedCentralGoogle Scholar
  139. Wang R, Chadalavada K, Wilshire J et al (2010b) Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468(7325):829–833PubMedCrossRefGoogle Scholar
  140. Weller M, Cloughesy T, Perry JR, Wick W (2012) Standards of care for treatment of recurrent glioblastoma—are we there yet? Neurooncology 2012Google Scholar
  141. Wolburg H, Lippoldt A (2002) Tight junctions of the blood–brain barrier: development, composition and regulation. Vasc Pharmacol 38(6):323–337CrossRefGoogle Scholar
  142. Yao X, Ping Y, Liu Y et al (2013) Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a key role in vasculogenic mimicry formation, neovascularization and tumor initiation by Glioma stem-like cells. PLoS One 8(3):e57188PubMedPubMedCentralCrossRefGoogle Scholar
  143. Yong RL, Lonser RR (2011) Surgery for glioblastoma multiforme: striking a balance. World Neurosurg 76(6):528–530PubMedPubMedCentralCrossRefGoogle Scholar
  144. Zhong H, De Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59(22):5830–5835PubMedGoogle Scholar
  145. Zhu Z, Hao X, Yan M et al (2010) Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer 126(9):2067–2078PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Anirudh Sattiraju
    • 1
  • Kiran Kumar Solingapuram Sai
    • 1
  • Akiva Mintz
    • 1
    Email author
  1. 1.Department of RadiologyColumbia University College of Physicians and SurgeonsNew YorkUSA

Personalised recommendations