Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

Home/2015, Vol. 3, No. 2/Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

Cell and Organ Transplantology. 2015; 3(2):177-183.
DOI: 10.22494/COT.V3I2.10

Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

Belska L. M., Lisyany M. I.
A. Romodanov State Institute of Neurosurgery NAMS of Ukraine, Kyiv, Ukraine

The review presents the current conceptions of the origin, methods of isolation and phenotypic characterization of the brain tumor stem cells. Phenotypic similarity in molecular markers between cancer and neural stem cells is shown. Therapeutic approaches of impact on the brain tumor stem cells and on the intracellular signaling pathways of cancer stem cells are described.

Key words: brain tumor stem cells, neural stem cells, malignant gliomas, CD133, nestin

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1. Bonnet D, Dick JF. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997; 3:730–737.
2. Reya T, Morrison SJ, Clarke IL. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414:105–111.
3. Clevers H. The cancer stem ceil: Premises, promises and challenges. Nat. Med. 2011; 17:313–319.
4. Suetsugu A, Nagaki M, Aokil H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 2006; 29(4):820–824.
5. Yuan X, Curtin J, Xiong Y, et al. Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene. 2004; 16(23):9392–9400.
6. Vescovi AL, Gall R, Reynolds BA. Brain tumour stem cells. Nat. Rev.Canser. 2006; 6:425–436.
7. Dalerba P, Cho RW, Clarke MF. Cancer stem cells: Models and concepts. Ann. Rev. Med. 2007; 58:267–284.
8. Wicha MS. Cancer stem cells and metastasis: Lethal seeds. Clin. Cancer. Res. 2006; 12:5606–5607.
9. Shiras A, Chettiar ST, Shepal V. Spontaneous transformation of human adult nontumorogenic stem sells to cancer stem cells is driven by gemonic instability in a human model of glioblastoma. Stem Cells. 2007; 25(6):1478–1489.
10. Masui K, Suzuki SO, Torisu R. Glial progenitors in the brainstem give rise to malignant gliomas by platelet–derived growth factor stimulation. Glia. 2010; 58(9):1050–1065.
11. Junier MP, Sharif A. Instability of cell phenotype and tumor initiating cells in gliomas. Biol. Aujordhui (French). 2011; 205(1):63–74.
12. Galli R, Binda E, Orfanelli U. Isolation and characterization of tumorigenic, stem–like neural precursors from human glioblastoma. Cancer Res. 2004; 1(19):7011–7021.
13. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003; 63:5821–5828.
14. Zhang M, Song T, Yang L, et al. Nestin and CD–133: valuable stem cell–specific markers for determing clinical outcome of glioma patients. J. Exp Clin Cancer Res. 2008; 24(27):85–92.
PMid:19108713 PMCid:PMC2633002
15. Pallini RL, Ricci–Vitiani L, Montano N. Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis. Cancer. 2011; 117(1):162–174.
16. Zeppernick F, Ahmadi R, Campos B, et al. Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res. 2008; 14:123–129.
17. Ma YH, Mentlein R, Knerlich F, et al. Expression of stem cell markers in human astrocytomas of different WHO grades. J. Neurooncol. 2008; 86:31–45.
18. Kim KJ, Lee KH, Kim HS, et al. The presence of stem cell marker–expressing cells is not prognostically significant in glioblastomas. Neuropathology. 2011; 31:494–502.
19. Lee J, Kotliarova S, Kotliarov Y, et al. 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.
20. Bo Qio, Zhang D, Tao J. A simplified and modified procedure to culture brain glioma stem cells from clinical specimens. Oncol Lett. 2012; 1:50–54.
21. Beier D, Hau P, Proescholdt M. CD133+ and CD133– glioblastoma–derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 2007; 17(9):4010–4015.
22. Choung YK, Toh TB, Zaiden N. Cryopreservation of neurosphtres derived from human glioblastoma multiforme. Stem Cells. 2009; 27(1):29–39.
PMid:18845764 PMCid:PMC2729678
23. Read TA, Fogarty MP, Markant SL, et al. Identification of CD15 as a marker for tumor–propagating cells in a mouse model of medulloblastoma. Cancer Cell. 2009; 15:135–147.
PMid:19185848 PMCid:PMC2664097
24. Son MJ, Woolard K, Nam DH, et al. SSEA–1 is an enrichment marker for tumorinitiating cells in human glioblastoma. Cell Stem Cell. 2009; 4:440–452.
25. He J, Liu Y, Zhuet T, et al. CD90 is identified as a marker for cancer stem cells in primary high–grade gliomas using tissue microarrays. Mol. Cell Proteomics. 2010; 11(6):M111.010744.
26. Tchoghandjian A, Baeza N, Colin C, et al. A2B5 cells from human glioblastoma have cancer stem cell properties. Brain Pathol. 2010; 20:211–221.
27. Piepmeier JM, Fried I, Makuch R. Low–grade astrocytomas may arise from different astrocyte lineages. Neurosurgery. 1993; 33:627–632.
28. Chinnaiyan P, Wang M, Rojiani AM, et al. The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group. Radiat Oncol. 2008; 3:32.
PMid:18817556 PMCid:PMC2563009
29. Wan F, Herold–Mende C, Campos B, et al. Association of stem cell–related markers and survival in astrocytic gliomas. Biomarker. 2011; 16:136–143.
30. Arai H, Ikota H, Sugawara K, et al. Nestin expression in brain tumors: its utility for pathological diagnosis and correlation with the prognosis of high–grade gliomas. Brain Tumor Pathol. 2012; 29:160–167.
31. Kim KJ, Lee KH, Kim HS, et al. The presence of stem cell marker–expressing cells is not prognostically significant in glioblastomas. Neuropathology. 2011; 31:494–502.
32. Gangemi RM, Griffero F, Marubbi D, et al. SOX2 silencing in glioblastoma tumor–initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells. 2009; 27:40–48.
33. Phi JH, Park SH, Kim SK, et al. Sox2 expression in brain tumors: a reflection of the neuroglial differentiation pathway. Am J Surg Pathol. 2008; 32:103–112.
34. Wan F, Herold–Mende C, Campos B, et al. Association of stem cell–related markers and survival in astrocytic gliomas. Biomarkers. 2011; 16:136–143.
35. Mishima K, Kato Y, Kaneko MK, et al. Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression. Acta Neuropathol. 2006; 111:483–488.
36. Venugopal C, Li N, Wang X, et al. Bmi1 marks intermediate precursors during differentiation of human brain tumor initiating cells. Stem Cell Res. 2012; 8:141–153.
37. Hayry V, Tynninen O, Haapasalo HK, et al. Stem cell protein BMI–1 is an independent marker for poor prognosis in oligodendroglial tumour. J. Neuropathol Appl Neurobiol. 2008; 34: 555–563.
38. Hemmati HD, Nakano I, Lazareff JA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003; 100:15178–15183.
PMid:14645703 PMCid:PMC299944
39. Ma YH, Mentlein R, Knerlich F, et al. Expression of stem cell markers in human astrocytomas of different WHO grades. J Neurooncol. 2008; 86:31–45.
40. Kanemura Y, Mori K, Sakakibara S, Fujikawa H, et al. Musashi1, an evolutionarily conserved neural RNA–binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity. Differentiation. 2001; 68:141–152.
41. Iavarone A, Lasorella A. ID proteins as targets in cancer and tools in neurobiology. Trends Mol Med. 2006; 12:88–594.
42. Phi JH, Kim JH, Eun KM, et al. Upregulation of SOX2, NOTCH1, and ID1 in supratentorial primitive neuroectodermal tumors: a distinct differentiation pattern from that of medulloblastomas. J Neurosurg Pediatr. 2010; 5:608–614.
43. Du Z, Jia D, Liu S, et al. Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia. 2009; 57:724–733.
44. Guo YL, Liu S, Wang P, et al. Expression profile of embryonic stem cell–associated genes Oct4, Sox2 and Nanog in human gliomas. Histopathology. 2011; 59(4):763–775.
45. Lottaz C, Beier D, Mayer K, et al. Transcriptional profiles of CD133+ and CD133–glioblastoma–derived cancer stem cell lines suggest different ctll of origin. Canser stem cell lines suggest different cell of origin Cancer Res. 2010; 70(5):2030–2040.
47. Jamal M, Rath BN, Tsang P, et al. The brain microenvironment preferentially enhances the radioresistance of CD 133(+) glioblastoma stem–like. Neoplasia. 2012; 14:150–158.
PMid:22431923 PMCid:PMC3306260
48. He J, Liu Y, Lubman D. Targeting glioblastoma stem cells: cell surface markers. Curr Med Chem. 2012; 19(35):6050–6055.
49. Lisyany NI. Immunologija i immunoterapija zlokachestvennyh gliom golovnogo mozga. [Immunology and Immunotherapy of malignant gliomas of the brain]. Serija «Nejroimmunologija». Kiev: Interservis – Series “Neuroimmunology”. Kiev: Interservice. 2011; 5: 240 p.
50. Purow MW, Haque BW, Noel RM, et al. Expression of Notch–1 and its ligands, Delta–like–1 and Jagged–1, is critical for glioma cell survival and proliferation. Cancer Res. 2005; 65(6):2353–2563.
51. Fan X, Mikolaenko I, Elhassan I, et al. Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 2004; 64(21):7787–7793.
52. Zhang XP, Zheng G, Zou L, et al. Notch activation promotes cell proliferation and the formation of neural stem cell–like colonies in human glioma cells. Mol Cell Biochem. 2008; 307:101–108.
53. Park Y, Rangel C, Reynolds MM, et al. Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division. Dev Bio. 2003; 253(2):247–257.
54. Becher OJ, Hambardzumyan D, Fomchenko EI, et al. Gli activity correlates with tumor grade in platelet–derived growth factor–induced gliomas. Cancer Res. 2008; 68(7):2241–2249.
55. Dahmane N, Sanchez P, Gitton Y, et al. The Sonic Hedgehog–Gli pathway regulates dorsal brain growth and tumorigenesis. Development. 2001; 128:5201–5212.
56. Clement V, Sanchez P, Tribolet N, et al. HEDGEHOG–GLI1 signaling regulates human glioma growth, cancer stem cell self–renewal, and tumorigenicity. Curr Biol: CB. 2007; 17:165–172.
PMid:17196391 PMCid:PMC1855204
57. Bar EE, Chaudhry A, Lin A, et al. Cyclopamine–mediated hedgehog pathway inhibition depletes stem–like cancer cells in glioblastoma. Stem Cells. 2007; 25:2524–2533.
PMid:17628016 PMCid:PMC2610257
58. Lie DC, Colamarino SA, Song HJ, et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature. 2005; 437(7063):1370–1375.
59. Pu P, Zhang Z, Kang C, et al. Downregulation of Wnt2 and betacatenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther. 2009; 16(4):351–361.
60. Yu JM, Jun ES, Jung JS, et al. Role of Wnt5a in the proliferation of human glioblastoma cells. Cancer Lett. 2007; 257:172–181.

Belska LM, Lisyany MI. Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches. Cell and Organ Transplantology. 2015; 3(2):177-183. doi: 10.22494/COT.V3I2.10

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