The utility and limitations of neurosphere assay, cd133 immunophenotyping and side population assay in glioma stem cell research

Brain Pathology

Volumn 20, Issue 5, 2010, Pages 877-889

  Wan, Feng ^a   Zhang, Suojun ^a   Xie, Ruifan ^a   Gao, Baocheng ^a   Campos, Benito ^b   Herold Mende, Christel ^b   Lei, Ting ^a  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

CD133; glioma; neurosphere; side population; stem cell

Indexed keywords

CD133 ANTIGEN;

CANCER STEM CELL; FLUORESCENCE ACTIVATED CELL SORTING; GLIOMA; IMMUNOPHENOTYPING; REVIEW; TUMOR BIOPSY;

ANIMALS; ANTIGENS, CD; BIOMEDICAL RESEARCH; GLIOMA; GLYCOPROTEINS; HUMANS; IMMUNOPHENOTYPING; NEOPLASTIC STEM CELLS; PEPTIDES;

EID: 77955158299     PISSN: 10156305     EISSN: 17503639     Source Type: Journal    
DOI: 10.1111/j.1750-3639.2010.00379.x     Document Type: Review

References (136)

1. Adamski D, Mayol JF, Platet N, Berger F, Herodin F, Wion D (2007) Effects of Hoechst 33342 on C2C12 and PC12 cell differentiation. FEBS Lett 581 : 3076 3080.
2. Asakura A, Seale P, Girgis-Gabardo A, Rudnicki MA (2002) Myogenic specification of side population cells in skeletal muscle. J Cell Biol 159 : 123 134.
3. Balenci L, Clarke ID, Dirks PB, Assard N, Ducray F, Jouvet A et al (2006) IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme. Cancer Res 66 : 9074 9082.
4. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444 : 756 760.
5. Bauer N, Fonseca AV, Florek M, Freund D, Jaszai J, Bornhauser M et al (2008) New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs 188 : 127 138.
6. Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ et al (2007) CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67 : 4010 4015.
7. Beier D, Wischhusen J, Dietmaier W, Hau P, Proescholdt M, Brawanski A et al (2008) CD133 expression and cancer stem cells predict prognosis in high-grade oligodendroglial tumors. Brain Pathol 18 : 370 377.
8. Bell HS, Whittle IR, Walker M, Leaver HA, Wharton SB (2001) The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems. Neuropathol Appl Neurobiol 27 : 291 304.
9. Ben-Hur T, Einstein O, Mizrachi-Kol R, Ben-Menachem O, Reinhartz E, Karussis D, Abramsky O (2003) Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis. Glia 41 : 73 80.
10. Bhatt RI, Brown MD, Hart CA, Gilmore P, Ramani VA, George NJ, Clarke NW (2003) Novel method for the isolation and characterisation of the putative prostatic stem cell. Cytometry A 54 : 89 99.
11. Bidlingmaier S, Zhu X, Liu B (2008) The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J Mol Med 86 : 1025 1032.
12. Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, Holland EC (2009) PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 4 : 226 235.
13. Bleau AM, Huse JT, Holland EC (2009) The ABCG2 resistance network of glioblastoma. Cell Cycle 8 : 2936 2944.
14. Bunting KD, Zhou S, Lu T, Sorrentino BP (2000) Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo. Blood 96 : 902 909.
15. Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11 : 69 82.
16. Carlsson J, Acker H (1988) Relations between pH, oxygen partial pressure and growth in cultured cell spheroids. Int J Cancer 42 : 715 720.
17. Chaichana K, Zamora-Berridi G, Camara-Quintana J, Quinones-Hinojosa A (2006) Neurosphere assays: growth factors and hormone differences in tumor and nontumor studies. Stem Cells 24 : 2851 2857.
18. Chaichana KL, Guerrero-Cazares H, Capilla-Gonzalez V, Zamora-Berridi G, Achanta P, Gonzalez-Perez O et al (2009) Intra-operatively obtained human tissue: protocols and techniques for the study of neural stem cells. J Neurosci Methods 180 : 116 125.
19. Challen GA, Little MH (2006) A side order of stem cells: the SP phenotype. Stem Cells 24 : 3 12.
20. Chen KA, Laywell ED, Marshall G, Walton N, Zheng T, Steindler DA (2006) Fusion of neural stem cells in culture. Exp Neurol 198 : 129 135.
21. Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A et al (2006) Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 44 : 240 251.
22. Chua C, Zaiden N, Chong KH, See SJ, Wong MC, Ang BT, Tang C (2008) Characterization of a side population of astrocytoma cells in response to temozolomide. J Neurosurg 109 : 856 866.
23. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL et al (2006) Cancer stem cells - perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66 : 9339 9344.
24. Clayton H, Titley I, Vivanco M (2004) Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res 297 : 444 460.
25. Clement V, Dutoit V, Marino D, Dietrich PY, Radovanovic I (2009) Limits of CD133 as a marker of glioma self-renewing cells. Int J Cancer 125 : 244 248.
26. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz IAA (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17 : 165 172.
27. Corbeil D, Roper K, Fargeas CA, Joester A, Huttner WB (2001) Prominin: a story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2 : 82 91.
28. Corbeil D, Roper K, Hellwig A, Tavian M, Miraglia S, Watt SM et al (2000) The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 275 : 5512 5520.
29. Cordey M, Limacher M, Kobel S, Taylor V, Lutolf MP (2008) Enhancing the reliability and throughput of neurosphere culture on hydrogel microwell arrays. Stem Cells 26 : 2586 2594.
30. Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5 : 275 284.
31. Dictus C, Tronnier V, Unterberg A, Herold-Mende C (2007) Comparative analysis of in vitro conditions for rat adult neural progenitor cells. J Neurosci Methods 161 : 250 258.
32. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97 : 703 716.
33. Fargeas CA, Huttner WB, Corbeil D (2007) Nomenclature of prominin-1 (CD133) splice variants - an update. Tissue Antigens 69 : 602 606.
34. Florek M, Haase M, Marzesco AM, Freund D, Ehninger G, Huttner WB, Corbeil D (2005) Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. Cell Tissue Res 319 : 15 26.
35. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64 : 7011 7021.
36. Green WB, Slovak ML, Chen IM, Pallavicini M, Hecht JL, Willman CL (1999) Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31). Leukemia 13 : 1960 1971.
37. Griguer CE, Oliva CR, Gobin E, Marcorelles P, Benos DJ, Lancaster JRJr, Gillespie GY (2008) CD133 is a marker of bioenergetic stress in human glioma. Plos One 3 : e3655.
38. Gritti A, Frolichsthal-Schoeller P, Galli R, Parati EA, Cova L, Pagano SF et al (1999) Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci 19 : 3287 3297.
39. Gritti A, Parati EA, Cova L, Frolichsthal P, Galli R, Wanke E et al (1996) Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor. J Neurosci 16 : 1091 1100.
40. Gunther HS, Schmidt NO, Phillips HS, Kemming D, Kharbanda S, Soriano R et al (2008) Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene 27 : 2897 2909.
41. Gutova M, Najbauer J, Frank RT, Kendall SE, Gevorgyan A, Metz MZ et al (2008) Urokinase plasminogen activator and urokinase plasminogen activator receptor mediate human stem cell tropism to malignant solid tumors. Stem Cells 26 : 1406 1413.
42. Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, Mori M (2006) Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 24 : 506 513.
43. Harris MA, Yang H, Low BE, Mukherje J, Guha A, Bronson RT et al (2008) Cancer stem cells are enriched in the side population cells in a mouse model of glioma. Cancer Res 68 : 10051 10059.
44. Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN (2009) The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 8 : 3274 3284.
45. Heese O, Disko A, Zirkel D, Westphal M, Lamszus K (2005) Neural stem cell migration toward gliomas in vitro. Neuro Oncol 7 : 476 484.
46. Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 100 : 15178 15183.
47. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U et al (2004) A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A 101 : 14228 14233.
48. Ho MM, Ng AV, Lam S, Hung JY (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67 : 4827 4833.
49. 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 : 193 206.
50. Iwatani H, Ito T, Imai E, Matsuzaki Y, Suzuki A, Yamato M et al (2004) Hematopoietic and nonhematopoietic potentials of Hoechst(low)/side population cells isolated from adult rat kidney. Kidney Int 65 : 1604 1614.
51. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, Alvarez-Buylla A (2006) PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51 : 187 199.
52. Jackson KA, Mi T, Goodell MA (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci U S A 96 : 14482 14486.
53. Jessberger S, Clemenson GD Jr., Gage FH (2007) Spontaneous fusion and nonclonal growth of adult neural stem cells. Stem Cells 25 : 871 874.
54. Jonker JW, Buitelaar M, Wagenaar E, Van Der Valk MA, Scheffer GL, Scheper RJ et al (2002) The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci U S A 99 : 15649 15654.
55. Jonker JW, Freeman J, Bolscher E, Musters S, Alvi AJ, Titley I et al (2005) Contribution of the ABC transporters Bcrp1 and Mdr1a/1b to the side population phenotype in mammary gland and bone marrow of mice. Stem Cells 23 : 1059 1065.
56. Joo KM, Kim SY, Jin X, Song SY, Kong DS, Lee JI et al (2008) Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas. Lab Invest 88 : 808 815.
57. Jurvansuu J, Zhao Y, Leung DS, Boulaire J, Yu YH, Ahmed S, Wang S (2008) Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells. Cancer Res 68 : 4614 4622.
58. Kawada H, Fujita J, Kinjo K, Matsuzaki Y, Tsuma M, Miyatake H et al (2004) Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood 104 : 3581 3587.
59. Kendall SE, Najbauer J, Johnston HF, Metz MZ, Li S, Bowers M et al (2008) Neural stem cell targeting of glioma is dependent on phosphoinositide 3-kinase signaling. Stem Cells 26 : 1575 1586.
60. Kim M, Morshead CM (2003) Distinct populations of forebrain neural stem and progenitor cells can be isolated using side-population analysis. J Neurosci 23 : 10703 10709.
61. Kondo T, Setoguchi T, Taga T (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A 101 : 781 786.
62. Kosodo Y, Roper K, Haubensak W, Marzesco AM, Corbeil D, Huttner WB (2004) Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO J 23 : 2314 2324.
63. Kubota H, Avarbock MR, Brinster RL (2003) Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci U S A 100 : 6487 6492.
64. Laks DR, Masterman-Smith M, Visnyei K, Angenieux B, Orozco NM, Foran I et al (2009) Neurosphere formation is an independent predictor of clinical outcome in malignant glioma. Stem Cells 27 : 980 987.
65. Lalande ME, Miller RG (1979) Fluorescence flow analysis of lymphocyte activation using Hoechst 33342 dye. J Histochem Cytochem 27 : 394 397.
66. Lantos PL, Pilkington GJ (1979) The development of experimental brain tumours. A sequential light and electron microscope study of the subependymal plate. I. Early lesions (abnormal cell clusters). Acta Neuropathol 45 : 167 175.
67. Lassalle B, Bastos H, Louis JP, Riou L, Testart J, Dutrillaux B et al (2004) "Side population" cells in adult mouse testis express Bcrp1 gene and are enriched in spermatogonia and germinal stem cells. Development 131 : 479 487.
68. Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM et al (2006) Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9 : 391 403.
69. Liu Q, Nguyen DH, Dong Q, Shitaku P, Chung K, Liu OY et al (2009) Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors. J Neurooncol 94 : 1 19.
70. Louis SA, Rietze RL, Deleyrolle L, Wagey RE, Thomas TE, Eaves AC, Reynolds BA (2008) Enumeration of neural stem and progenitor cells in the neural colony-forming cell assay. Stem Cells 26 : 988 996.
71. Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S et al (2004) Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 265 : 262 275.
72. Marzesco AM, Janich P, Wilsch-Brauninger M, Dubreuil V, Langenfeld K, Corbeil D, Huttner WB (2005) Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci 118 : 2849 2858.
73. Matsuda M, Imaoka T, Vomachka AJ, Gudelsky GA, Hou Z, Mistry M et al (2004) Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev Cell 6 : 193 203.
74. Maw MA, Corbeil D, Koch J, Hellwig A, Wilson-Wheeler JC, Bridges RJ et al (2000) A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum Mol Genet 9 : 27 34.
75. 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 : 489 497.
76. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT et al (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90 : 5013 5021.
77. Mizrak D, Brittan M, Alison MR (2008) CD133: molecule of the moment. J Pathol 214 : 3 9.
78. Montanaro F, Liadaki K, Schienda J, Flint A, Gussoni E, Kunkel LM (2004) Demystifying SP cell purification: viability, yield, and phenotype are defined by isolation parameters. Exp Cell Res 298 : 144 154.
79. Mori H, Kanemura Y, Onaya J, Hara M, Miyake J, Yamasaki M, Kariya Y (2005) Effects of heparin and its 6-O-and 2-O-desulfated derivatives with low anticoagulant activity on proliferation of human neural stem/progenitor cells. J Biosci Bioeng 100 : 54 61.
80. Mori H, Ninomiya K, Kino-oka M, Shofuda T, Islam MO, Yamasaki M et al (2006) Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. J Neurosci Res 84 : 1682 1691.
81. Ogden AT, Waziri AE, Lochhead RA, Fusco D, Lopez K, Ellis JA et al (2008) Identification of A2B5+ CD133- tumor-initiating cells in adult human gliomas. Neurosurgery 62 : 505 514, discussion 514-515.
82. Parker MA, Anderson JK, Corliss DA, Abraria VE, Sidman RL, Park KI et al (2005) Expression profile of an operationally-defined neural stem cell clone. Exp Neurol 194 : 320 332.
83. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG (2005) Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res 65 : 6207 6219.
84. Persson AI, Weiss WA (2009) The side story of stem-like glioma cells. Cell Stem Cell 4 : 191 192.
85. Pfenninger CV, Roschupkina T, Hertwig F, Kottwitz D, Englund E, Bengzon J et al (2007) CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells. Cancer Res 67 : 5727 5736.
86. Platet N, Liu SY, Atifi ME, Oliver L, Vallette FM, Berger F, Wion D (2007) Influence of oxygen tension on CD133 phenotype in human glioma cell cultures. Cancer Lett 258 : 286 290.
87. Pollard SM, Conti L, Sun Y, Goffredo D, Smith A (2006) Adherent neural stem (NS) cells from fetal and adult forebrain. Cereb Cortex 16 (Suppl. 1 i112 120.
88. Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R et al (2009) Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4 : 568 580.
89. Qiang L, Yang Y, Ma YJ, Chen FH, Zhang LB, Liu W et al (2009) Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett 279 : 13 21.
90. Reynolds BA, Rietze RL (2005) Neural stem cells and neurospheres - re-evaluating the relationship. Nat Methods 2 : 333 336.
91. Reynolds BA, Vescovi AL (2009) Brain cancer stem cells: think twice before going flat. Cell Stem Cell 5 : 466 467. author reply 468-469.
92. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255 : 1707 1710.
93. Reynolds BA, Weiss S (1996) Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 175 : 1 13.
94. Sakariassen PO, Immervoll H, Chekenya M (2007) Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia 9 : 882 892.
95. Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S et al (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427 : 740 744.
96. Schinkel AH, Smit JJ, van TO, Beijnen JH, Wagenaar E, van DL (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77 : 491 502.
97. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB et al (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22 : 1115 1124.
98. Shimano K, Satake M, Okaya A, Kitanaka J, Kitanaka N, Takemura M et al (2003) Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1. Am J Pathol 163 : 3 9.
99. Shmelkov SV, Jun L, St Clair R, McGarrigle D, Derderian CA, Usenko JK et al (2004) Alternative promoters regulate transcription of the gene that encodes stem cell surface protein AC133. Blood 103 : 2055 2061.
100. Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT et al (2008) Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 26 : 1414 1424.
101. Singec I, Knoth R, Meyer RP, Maciaczyk J, Volk B, Nikkhah G et al (2006) Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biology. Nat Methods 3 : 801 806.
102. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63 : 5821 5828.
103. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al (2004) Identification of human brain tumour initiating cells. Nature 432 : 396 401.
104. Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD et al (2009) Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene 28 : 3949 3959.
105. 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 : 440 452.
106. Srivastava VK, Nalbantoglu J (2008) Flow cytometric characterization of the DAOY medulloblastoma cell line for the cancer stem-like phenotype. Cytometry A 73 : 940 948.
107. Steuer B, Breuer B, Alonso A (1990) Differentiation of EC cells in vitro by the fluorescent dye Hoechst 33342. Exp Cell Res 186 : 149 157.
108. Storms RW, Goodell MA, Fisher A, Mulligan RC, Smith C (2000) Hoechst dye efflux reveals a novel CD7(+)CD34(-) lymphoid progenitor in human umbilical cord blood. Blood 96 : 2125 2133.
109. Summer R, Kotton DN, Sun X, Fitzsimmons K, Fine A (2004) Translational physiology: origin and phenotype of lung side population cells. Am J Physiol Lung Cell Mol Physiol 287 : L477 L483.
110. Sun Y, Kong W, Falk A, Hu J, Zhou L, Pollard S, Smith A (2009) CD133 (prominin) negative human neural stem cells are clonogenic and tripotent. Plos One 4 : e5498.
111. Sun Y, Pollard S, Conti L, Toselli M, Biella G, Parkin G et al (2008) Long-term tripotent differentiation capacity of human neural stem (NS) cells in adherent culture. Mol Cell Neurosci 38 : 245 258.
112. Suslov ON, Kukekov VG, Ignatova TN, Steindler DA (2002) Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc Natl Acad Sci U S A 99 : 14506 14511.
113. Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, Caldwell MA (1998) A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods 85 : 141 152.
114. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R et al (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian inhibiting substance responsiveness. Proc Natl Acad Sci U S A 103 : 11154 11159.
115. Tchoghandjian A, Baeza N, Colin C, Cayre M, Metellus P, Beclin C et al (2009) A2B5 cells from human glioblastoma have cancer stem cell properties. Brain Pathol [E-pub ahead of print; doi:10.1111/j.1750-3639.2009.00269.x].
116. Terunuma A, Jackson KL, Kapoor V, Telford WG, Vogel JC (2003) Side population keratinocytes resembling bone marrow side population stem cells are distinct from label-retaining keratinocyte stem cells. J Invest Dermatol 121 : 1095 1103.
117. Tirino V, Desiderio V, d'Aquino R, De Francesco F, Pirozzi G, Graziano A et al (2008) Detection and characterization of CD133+ cancer stem cells in human solid tumours. Plos One 3 : e3469.
118. Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD (2001) Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 3 : 778 784.
119. Triel C, Vestergaard ME, Bolund L, Jensen TG, Jensen UB (2004) Side population cells in human and mouse epidermis lack stem cell characteristics. Exp Cell Res 295 : 79 90.
120. Uhrbom L, Kastemar M, Johansson FK, Westermark B, Holland EC (2005) Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis. Cancer Res 65 : 2065 2069.
121. Varghese M, Olstorn H, Sandberg C, Vik-Mo EO, Noordhuis P, Nister M et al (2008) A comparison between stem cells from the adult human brain and from brain tumors. Neurosurgery 63 : 1022 1033, discussion 1033-1034.
122. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6 : 425 436.
123. Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67 : 3716 3724.
124. Wang J, Sakariassen PO, Tsinkalovsky O, Immervoll H, Boe SO, Svendsen A et al (2008) CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int J Cancer 122 : 761 768.
125. Watanabe K, Nishida K, Yamato M, Umemoto T, Sumide T, Yamamoto K et al (2004) Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2. FEBS Lett 565 : 6 10.
126. Weigmann A, Corbeil D, Hellwig A, Huttner WB (1997) Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci U S A 94 : 12425 12430.
127. Woolard K, Fine HA (2009) Glioma stem cells: better flat than round. Cell Stem Cell 4 : 466 467.
128. Wu C, Alman BA (2008) Side population cells in human cancers. Cancer Lett 268 : 1 9.
129. Wu C, Wei Q, Utomo V, Nadesan P, Whetstone H, Kandel R et al (2007) Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res 67 : 8216 8222.
130. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG et al (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90 : 5002 5012.
131. Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL et al (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23 : 9392 9400.
132. Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N et al (2008) Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 14 : 123 129.
133. Zheng X, Shen G, Yang X, Liu W (2007) Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res 67 : 3691 3697.
134. Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J et al (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A 104 : 16158 16163.
135. Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP (2002) Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci U S A 99 : 12339 12344.
136. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ et al (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7 : 1028 1034.