Cancer Stem Cells in Tumor Heterogeneity

Advances in Cancer Research

Volumn 112, Issue , 2011, Pages 255-281

  Pietras, Alexander ^a  

^a LUND UNIVERSITY   (Sweden)

Author keywords

Angiogenesis; Invasive; Lesion; Metastatic; Migratory; Phenotypic

Indexed keywords

ADAPALENE; BREAST CANCER RESISTANCE PROTEIN; CD133 ANTIGEN; CD24 ANTIGEN; CD34 ANTIGEN; CD38 ANTIGEN; CD44V ANTIGEN; NOTCH RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR; PROTEIN KINASE B; TEMOZOLOMIDE; TRANSCRIPTION FACTOR SOX10; VASCULOTROPIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANGIOGENESIS; BOOK; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER STEM CELL; CELL CYCLE ARREST; CELL DIFFERENTIATION; CELL HETEROGENEITY; CELL PROLIFERATION; CHEMORADIOTHERAPY; CHILDHOOD CANCER; CHROMOSOMAL INSTABILITY; CHROMOSOME ABERRATION; CLINICAL EFFECTIVENESS; CLINICAL FEATURE; CLONE; DNA DAMAGE; DNA REPAIR; GLIOBLASTOMA; HIGH INTENSITY FOCUSED ULTRASOUND; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; LYMPHATIC LEUKEMIA; MEDULLOBLASTOMA; MELANOMA; METASTASIS; NEUROBLASTOMA; NONHUMAN; ONCOGENE C MYB; OXYGEN TENSION; PRIMARY TUMOR; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; SINGLE NUCLEOTIDE POLYMORPHISM; SOLID TUMOR; STEM CELL TRANSPLANTATION; STOMACH CANCER; TREATMENT RESPONSE; TUMOR GROWTH; TUMOR VASCULARIZATION; TUMOR XENOGRAFT; XENOTRANSPLANTATION;

EID: 80052974307     PISSN: 0065230X     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-387688-1.00009-0     Document Type: Chapter

References (116)

1. Aboody K.S., Brown A., Rainov N.G., Bower K.A., Liu S., Yang W., Small J.E., Herrlinger U., Ourednik V., Black P.M., Breakefield X.O., Snyder E.Y. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:12846-12851.
2. Albanese I., Scibetta A.G., Migliavacca M., Russo A., Bazan V., Tomasino R.M., Colomba P., Tagliavia M., La Farina M. Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations. Biochem. Biophys. Res. Commun. 2004, 325:784-791.
3. Al-Hajj M., Becker M.W., Wicha M., Weissman I., Clarke M.F. Therapeutic implications of cancer stem cells. Curr. Opin. Genet. Dev. 2004, 14:43-47.
4. Al-Hajj M., Clarke M.F. Self-renewal and solid tumor stem cells. Oncogene 2004, 23:7274-7282.
5. Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S.J., Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:3983-3988.
6. Artale S., Sartore-Bianchi A., Veronese S.M., Gambi V., Sarnataro C.S., Gambacorta M., Lauricella C., Siena S. Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J. Clin. Oncol. 2008, 26:4217-4219.
7. Assanah M., Lochhead R., Ogden A., Bruce J., Goldman J., Canoll P. Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J. Neurosci. 2006, 26:6781-6790.
8. Axelson H., Fredlund E., Ovenberger M., Landberg G., Påhlman S. Hypoxia-induced dedifferentiation of tumor cells-a mechanism behind heterogeneity and aggressiveness of solid tumors. Semin. Cell. Dev. Biol. 2005, 16:554-563.
9. Bao S., Wu Q., McLendon R.E., Hao Y., Shi Q., Hjelmeland A.B., Dewhirst M.W., Bigner D.D., Rich J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006 a, 444:756-760.
10. Bao S., Wu Q., Sathornsumetee S., Hao Y., Li Z., Hjelmeland A.B., Shi Q., McLendon R.E., Bigner D.D., Rich J.N. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006 b, 66:7843-7848.
11. Bar E.E., Lin A., Mahairaki V., Matsui W., Eberhart C.G. Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres. Am. J. Pathol. 2010, 177:1491-1502.
12. Bexell D., Scheding S., Bengzon J. Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectors. Mol. Ther. 2010, 18:1067-1075.
13. Birnbaum T., Roider J., Schankin C.J., Padovan C.S., Schichor C., Goldbrunner R., Straube A. Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J. Neurooncol. 2007, 83:241-247.
14. Bissell M.J. Tumor plasticity allows vasculogenic mimicry, a novel form of angiogenic switch. A rose by any other name?. Am. J. Pathol. 1999, 155:675-679.
15. Bleau A.M., Hambardzumyan D., Ozawa T., Fomchenko E.I., Huse J.T., Brennan C.W., Holland E.C. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 2009, 4:226-235.
16. Calabrese C., Poppleton H., Kocak M., Hogg T.L., Fuller C., Hamner B., Oh E.Y., Gaber M.W., Finklestein D., Allen M., Frank A., Bayazitov I.T., Zakharenko S.S., Gajjar A., Davidoff A., Gilbertson R.J. A perivascular niche for brain tumor stem cells. Cancer Cell 2007, 11:69-82.
17. Campbell L.L., Polyak K. Breast tumor heterogeneity: cancer stem cells or clonal evolution?. Cell Cycle 2007, 6:2332-2338.
18. Chappell J., Dalton S. Altered cell cycle regulation helps stem-like carcinoma cells resist apoptosis. BMC Biol. 2010, 8:63.
19. Charles N., Ozawa T., Squatrito M., Bleau A.M., Brennan C.W., Hambardzumyan D., Holland E.C. Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell. 2010, 6:141-152.
20. Chen J., Imanaka N., Griffin J.D. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J. Cancer. 2010, 102:351-360.
21. Civenni G., Walter A., Kobert N., Mihic-Probst D., Zipser M., Belloni B., Seifert B., Moch H., Dummer R., van den Broek M., Sommer L. Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth. Cancer Res 2011, 71(8):3098-3109.
22. Cohnheim J. Congenitales, quergestreiftes Muskelsarkom der Nieren. Virchows Archiv. 1875, 65:64-69.
23. Creighton C.J., Li X., Landis M., Dixon J.M., Neumeister V.M., Sjolund A., Rimm D.L., Wong H., Rodriguez A., Herschkowitz J.I., Fan C., Zhang X., He X., Pavlick A., Gutierrez M.C., Renshaw L., Larionov A.A., Faratian D., Hilsenbeck S.G., Perou C.M., Lewis M.T., Rosen J.M., Chang J.C. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:13820-13825.
24. Dai C., Celestino J.C., Okada Y., Louis D.N., Fuller G.N., Holland E.C. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 2001, 15:1913-1925.
25. Delahunt B. Sarcomatoid renal carcinoma: the final common dedifferentiation pathway of renal epithelial malignancies. Pathology 1999, 31:185-190.
26. DiMeo T.A., Anderson K., Phadke P., Fan C., Perou C.M., Naber S., Kuperwasser C. A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer. Cancer Res. 2009, 69:5364-5373.
27. Edsjo A., Holmquist L., Påhlman S. Neuroblastoma as an experimental model for neuronal differentiation and hypoxia-induced tumor cell dedifferentiation. Semin. Cancer Biol. 2007, 17:248-256.
28. Eliasz S., Liang S., Chen Y., De Marco M.A., Machek O., Skucha S., Miele L., Bocchetta M. Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by activating the IGF-1R pathway. Oncogene 2010, 29:2488-2498.
29. Eramo A., Lotti F., Sette G., Pilozzi E., Biffoni M., Di Virgilio A., Conticello C., Ruco L., Peschle C., De Maria R. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death. Differ. 2008, 15:504-514.
30. Fomchenko E.I., Holland E.C. Stem cells and brain cancer. Exp. Cell Res. 2005, 306:323-329.
31. Fujii H., Marsh C., Cairns P., Sidransky D., Gabrielson E. Genetic divergence in the clonal evolution of breast cancer. Cancer Res. 1996, 56:1493-1497.
32. Gerdes M.J., Yuspa S.H. The contribution of epidermal stem cells to skin cancer. Stem Cell. Rev. 2005, 1:225-231.
33. Giannoni E., Bianchini F., Masieri L., Serni S., Torre E., Calorini L., Chiarugi P. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res. 2010, 70:6945-6956.
34. Goodell M.A., McKinney-Freeman S., Camargo F.D. Isolation and characterization of side population cells. Methods Mol. Biol. 2005, 290:343-352.
35. Guarino M., Rubino B., Ballabio G. The role of epithelial-mesenchymal transition in cancer pathology. Pathology 2007, 39:305-318.
36. Gupta P.B., Chaffer C.L., Weinberg R.A. Cancer stem cells: mirage or reality?. Nat. Med. 2009, 15:1010-1012.
37. Gustafsson M.V., Zheng X., Pereira T., Gradin K., Jin S., Lundkvist J., Ruas J.L., Poellinger L., Lendahl U., Bondesson M. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev. Cell. 2005, 9:617-628.
38. Hambardzumyan D., Becher O.J., Holland E.C. Cancer stem cells and survival pathways. Cell Cycle 2008 a, 7:1371-1378.
39. Hambardzumyan D., Becher O.J., Rosenblum M.K., Pandolfi P.P., Manova-Todorova K., Holland E.C. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev. 2008 b, 22:436-448.
40. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell 2000, 100:57-70.
41. Heddleston J.M., Li Z., McLendon R.E., Hjelmeland A.B., Rich J.N. The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 2009, 8:3274-3284.
42. Helczynska K., Kronblad A., Jögi A., Nilsson E., Beckman S., Landberg G., Påhlman S. Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ. Cancer Res. 2003, 63:1441-1444.
43. Heppner G.H. Tumor heterogeneity. Cancer Res. 1984, 44:2259-2265.
44. Hermann P.C., Huber S.L., Herrler T., Aicher A., Ellwart J.W., Guba M., Bruns C.J., Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007, 1:313-323.
45. Holland E.C. Progenitor cells and glioma formation. Curr. Opin. Neurol. 2001, 14:683-688.
46. Houghton J., Stoicov C., Nomura S., Rogers A.B., Carlson J., Li H., Cai X., Fox J.G., Goldenring J.R., Wang T.C. Gastric cancer originating from bone marrow-derived cells. Science 2004, 306:1568-1571.
47. Hubbard S.A., Gargett C.E. A cancer stem cell origin for human endometrial carcinoma?. Reproduction 2010, 140:23-32.
48. Huse J.T., Holland E.C. Genetically engineered mouse models of brain cancer and the promise of preclinical testing. Brain Pathol. 2009, 19:132-143.
49. Jögi A., Ora I., Nilsson H., Lindeheim A., Makino Y., Poellinger L., Axelson H., Påhlman S. Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:7021-7026.
50. Jögi A., Vallon-Christersson J., Holmquist L., Axelson H., Borg A., Påhlman S. Human neuroblastoma cells exposed to hypoxia: induction of genes associated with growth, survival, and aggressive behavior. Exp. Cell Res. 2004, 295:469-487.
51. Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008, 321:1801-1816.
52. Kalikaki A., Koutsopoulos A., Trypaki M., Souglakos J., Stathopoulos E., Georgoulias V., Mavroudis D., Voutsina A. Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br. J. Cancer 2008, 99:923-929.
53. Katona T.M., Jones T.D., Wang M., Eble J.N., Billings S.D., Cheng L. Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma. Am. J. Surg. Pathol. 2007, 31:1029-1037.
54. Kim C.F., Jackson E.L., Woolfenden A.E., Lawrence S., Babar I., Vogel S., Crowley D., Bronson R.T., Jacks T. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005, 121:823-835.
55. Kim Y., Lin Q., Zelterman D., Yun Z. Hypoxia-regulated delta-like 1 homologue enhances cancer cell stemness and tumorigenicity. Cancer Res. 2009, 69:9271-9280.
56. Kuukasjarvi T., Karhu R., Tanner M., Kahkonen M., Schaffer A., Nupponen N., Pennanen S., Kallioniemi A., Kallioniemi O.P., Isola J. Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res. 1997, 57:1597-1604.
57. Lapidot T., Sirard C., Vormoor J., Murdoch B., Hoang T., Caceres-Cortes J., Minden M., Paterson B., Caligiuri M.A., Dick J.E. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994, 367:645-648.
58. Lee J., Kotliarova S., Kotliarov Y., Li A., Su Q., Donin N.M., Pastorino S., Purow B.W., Christopher N., Zhang W., Park J.K., Fine H.A. 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 2006, 9:391-403.
59. Li A., Zhou J., Zuckerman D., Rue M., Dalton V., Lyons C., Silverman L.B., Sallan S.E., Gribben J.G. Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection. Blood 2003, 102:4520-4526.
60. Li Z., Bao S., Wu Q., Wang H., Eyler C., Sathornsumetee S., Shi Q., Cao Y., Lathia J., McLendon R.E., Hjelmeland A.B., Rich J.N. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 2009, 15:501-513.
61. Liu H., Patel M.R., Prescher J.A., Patsialou A., Qian D., Lin J., Wen S., Chang Y.F., Bachmann M.H., Shimono Y., Dalerba P., Adorno M., Lobo N., Bueno J., Dirbas F.M., Goswami S., Somlo G., Condeelis J., Contag C.H., Gambhir S.S., Clarke M.F. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:18115-18120.
62. Lopez-Novoa J.M., Nieto M.A. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol. Med. 2009, 1:303-314.
63. Ma X.J., Salunga R., Tuggle J.T., Gaudet J., Enright E., McQuary P., Payette T., Pistone M., Stecker K., Zhang B.M., Zhou Y.X., Varnholt H., Smith B., Gadd M., Chatfield E., Kessler J., Baer T.M., Erlander M.G., Sgroi D.C. Gene expression profiles of human breast cancer progression. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:5974-5979.
64. Mani S.A., Guo W., Liao M.J., Eaton E.N., Ayyanan A., Zhou A.Y., Brooks M., Reinhard F., Zhang C.C., Shipitsin M., Campbell L.L., Polyak K., Brisken C., Yang J., Weinberg R.A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704-715.
65. Maniotis A.J., Folberg R., Hess A., Seftor E.A., Gardner L.M., Pe'er J., Trent J.M., Meltzer P.S., Hendrix M.J. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am. J. Pathol. 1999, 155:739-752.
66. Marusyk A., Polyak K. Tumor heterogeneity: Causes and consequences. Biochim. Biophys. Acta 2009.
67. Mendez O., Zavadil J., Esencay M., Lukyanov Y., Santovasi D., Wang S.C., Newcomb E.W., Zagzag D. 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 2010, 9:133.
68. Momota H., Holland E.C. Mouse models of CNS embryonal tumors. Brain Tumor Pathol. 2009, 26:43-50.
69. Moore N., Lyle S. Quiescent, slow-cycling stem cell populations in cancer: a review of the evidence and discussion of significance. J. Oncol 2011, 2011:396076.
70. Mullighan C.G., Phillips L.A., Su X., Ma J., Miller C.B., Shurtleff S.A., Downing J.R. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 2008, 322:1377-1380.
71. Noguera-Troise I., Daly C., Papadopoulos N.J., Coetzee S., Boland P., Gale N.W., Lin H.C., Yancopoulos G.D., Thurston G. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 2006, 444:1032-1037.
72. Notta F., Mullighan C.G., Wang J.C., Poeppl A., Doulatov S., Phillips L.A., Ma J., Minden M.D., Downing J.R., Dick J.E. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature 2011, 469:362-367.
73. Nowell P.C. The clonal evolution of tumor cell populations. Science 1976, 194:23-28.
74. O'Brien C.A., Pollett A., Gallinger S., Dick J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007, 445:106-110.
75. Osawa M., Hanada K., Hamada H., Nakauchi H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996, 273:242-245.
76. Park S.Y., Gonen M., Kim H.J., Michor F., Polyak K. Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J. Clin. Invest. 2010, 120:636-644.
77. Patrawala L., Calhoun T., Schneider-Broussard R., Li H., Bhatia B., Tang S., Reilly J.G., Chandra D., Zhou J., Claypool K., Coghlan L., Tang D.G. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 2006, 25:1696-1708.
78. Pezzolo A., Parodi F., Corrias M.V., Cinti R., Gambini C., Pistoia V. Tumor origin of endothelial cells in human neuroblastoma. J. Clin. Oncol. 2007, 25:376-383.
79. Phng L.K., Gerhardt H. Angiogenesis: a team effort coordinated by notch. Dev. Cell. 2009, 16:196-208.
80. Pietras A., Gisselsson D., Ora I., Noguera R., Beckman S., Navarro S., Påhlman S. High levels of HIF-2alpha highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche. J. Pathol. 2008, 214:482-488.
81. Pietras A., Johnsson A.S., Påhlman S. The HIF-2alpha-driven pseudo-hypoxic phenotype in tumor aggressiveness, differentiation, and vascularization. Curr. Top Microbiol. Immunol. 2010, 345:1-20.
82. Pietras A., von Stedingk K., Lindgren D., Påhlman S., Axelson H. JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation. Mol Cancer Res. 2011, 10.1158/1541-7786.MCR-10-0508.
83. Pistollato F., Abbadi S., Rampazzo E., Persano L., Della Puppa A., Frasson C., Sarto E., Scienza R., D'Avella D., Basso G. Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells 2010 a, 28:851-862.
84. Pistollato F., Rampazzo E., Persano L., Abbadi S., Frasson C., Denaro L., D'Avella D., Panchision D.M., Della Puppa A., Scienza R., Basso G. Interaction of HIF1alpha and notch signaling regulates medulloblastoma precursor proliferation and fate. Stem Cells 2010 b, 28(11):1918-1929.
85. Quintana E., Shackleton M., Foster H.R., Fullen D.R., Sabel M.S., Johnson T.M., Morrison S.J. Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell. 2010, 18:510-523.
86. Quintana E., Shackleton M., Sabel M.S., Fullen D.R., Johnson T.M., Morrison S.J. Efficient tumour formation by single human melanoma cells. Nature 2008, 456:593-598.
87. Reynolds B.A., Weiss S. Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev. Biol. 1996, 175:1-13.
88. Ricci-Vitiani L., Lombardi D.G., Pilozzi E., Biffoni M., Todaro M., Peschle C., De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature 2007, 445:111-115.
89. Ricci-Vitiani L., Pallini R., Biffoni M., Todaro M., Invernici G., Cenci T., Maira G., Parati E.A., Stassi G., Larocca L.M., De Maria R. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 2010, 468:824-828.
90. Ricci-Vitiani L., Pallini R., Larocca L.M., Lombardi D.G., Signore M., Pierconti F., Petrucci G., Montano N., Maira G., De Maria R. Mesenchymal differentiation of glioblastoma stem cells. Cell Death Differ. 2008, 15:1491-1498.
91. Ridgway J., Zhang G., Wu Y., Stawicki S., Liang W.C., Chanthery Y., Kowalski J., Watts R.J., Callahan C., Kasman I., Singh M., Chien M., Tan C., Hongo J.A., de Sauvage F., Plowman G., Yan M. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 2006, 444:1083-1087.
92. Sahlgren C., Gustafsson M.V., Jin S., Poellinger L., Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:6392-6397.
93. Santisteban M., Reiman J.M., Asiedu M.K., Behrens M.D., Nassar A., Kalli K.R., Haluska P., Ingle J.N., Hartmann L.C., Manjili M.H., Radisky D.C., Ferrone S., Knutson K.L. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009, 69:2887-2895.
94. Schatton T., Murphy G.F., Frank N.Y., Yamaura K., Waaga-Gasser A.M., Gasser M., Zhan Q., Jordan S., Duncan L.M., Weishaupt C., Fuhlbrigge R.C., Kupper T.S., Sayegh M.H., Frank M.H. Identification of cells initiating human melanomas. Nature 2008, 451:345-349.
95. Seidel S., Garvalov B.K., Wirta V., von Stechow L., Schanzer A., Meletis K., Wolter M., Sommerlad D., Henze A.T., Nister M., Reifenberger G., Lundeberg J., Frisen J., Acker T. A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain 2010, 133:983-995.
96. Sell S. On the stem cell origin of cancer. Am. J. Pathol. 2010, 176:2584-2594.
97. Shah N.P., Sawyers C.L. Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. Oncogene 2003, 22:7389-7395.
98. Shipitsin M., Campbell L.L., Argani P., Weremowicz S., Bloushtain-Qimron N., Yao J., Nikolskaya T., Serebryiskaya T., Beroukhim R., Hu M., Halushka M.K., Sukumar S., Parker L.M., Anderson K.S., Harris L.N., Garber J.E., Richardson A.L., Schnitt S.J., Nikolsky Y., Gelman R.S., Polyak K. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11:259-273.
99. Shupe T., Petersen B.E. Evidence regarding a stem cell origin of hepatocellular carcinoma. Stem Cell Rev. 2005, 1:261-264.
100. Siekmann A.F., Lawson N.D. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature 2007, 445:781-784.
101. Singh A., Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010, 29:4741-4751.
102. Singh S.K., Hawkins C., Clarke I.D., Squire J.A., Bayani J., Hide T., Henkelman R.M., Cusimano M.D., Dirks P.B. Identification of human brain tumour initiating cells. Nature 2004, 432:396-401.
103. Snippert H.J., van der Flier L.G., Sato T., van Es J.H., van den Born M., Kroon-Veenboer C., Barker N., Klein A.M., van Rheenen J., Simons B.D., Clevers H. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 2010, 143:134-144.
104. Southam C., Brunschwig A. Quantitative studies of autotransplantation of human cancer. Cancer 1961, 14:461-463.
105. Sullivan N.J., Sasser A.K., Axel A.E., Vesuna F., Raman V., Ramirez N., Oberyszyn T.M., Hall B.M. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene 2009, 28:2940-2947.
106. Taylor M.D., Poppleton H., Fuller C., Su X., Liu Y., Jensen P., Magdaleno S., Dalton J., Calabrese C., Board J., Macdonald T., Rutka J., Guha A., Gajjar A., Curran T., Gilbertson R.J. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell. 2005, 8:323-335.
107. Thurston G., Noguera-Troise I., Yancopoulos G.D. The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat. Rev. Cancer 2007, 7:327-331.
108. Visvader J.E. Cells of origin in cancer. Nature 2011, 469:314-322.
109. Wang R., Chadalavada K., Wilshire J., Kowalik U., Hovinga K.E., Geber A., Fligelman B., Leversha M., Brennan C., Tabar V. Glioblastoma stem-like cells give rise to tumour endothelium. Nature 2010, 468:829-833.
110. Waters D., Newman B., Levy M.L. Stem cell origin of brain tumors. Adv. Exp. Med. Biol. 2010, 671:58-66.
111. Weber T., Baier V., Pauly R., Sahay A., Baur M., Herrmann E., Ciccolini F., Hen R., Kronenberg G., Bartsch D. Inducible gene expression in GFAP+ progenitor cells of the SGZ and the dorsal wall of the SVZ-A novel tool to manipulate and trace adult neurogenesis. Glia. 2011, 59:615-626.
112. Wei X., Dombkowski D., Meirelles K., Pieretti-Vanmarcke R., Szotek P.P., Chang H.L., Preffer F.I., Mueller P.R., Teixeira J., MacLaughlin D.T., Donahoe P.K. Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:18874-18879.
113. Weigelt B., Glas A.M., Wessels L.F., Witteveen A.T., Peterse J.L., van't Veer L.J. Gene expression profiles of primary breast tumors maintained in distant metastases. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:15901-15905.
114. Yustein J.T., Liu Y.C., Gao P., Jie C., Le A., Vuica-Ross M., Chng W.J., Eberhart C.G., Bergsagel P.L., Dang C.V. Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:3534-3539.
115. Zeng Q., Li S., Chepeha D.B., Giordano T.J., Li J., Zhang H., Polverini P.J., Nor J., Kitajewski J., Wang C.Y. Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer Cell. 2005, 8:13-23.
116. Zuna J., Ford A.M., Peham M., Patel N., Saha V., Eckert C., Kochling J., Panzer-Grumayer R., Trka J., Greaves M. TEL deletion analysis supports a novel view of relapse in childhood acute lymphoblastic leukemia. Clin. Cancer Res. 2004, 10:5355-5360.