Functional Assays for Detection of Cancer Stem Cells

Česká verzia

Authors: J. Škoda ^1,2; J. Neradil ^1,3; R. Veselska ^1,2
Authors place of work: Laboratoř nádorové biologie, Ústav experimentální biologie, Přírodovědecká fakulta MU, Brno ¹; Klinika dětské onkologie LF MU a FN Brno ²; Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno ³
Published in the journal: Klin Onkol 2014; 27(Supplementum): 42-47

Summary

Cancer stem cells (CSCs) are considered to be a population of tumor cells, which are responsible for tumor initiation and progression. They are also involved in metastasizing and may be a possible cause of multidrug resistance and tumor recurrence. CSCs possess the ability to self‑ renew and show a tumorigenic potential. Functional assays, which enable the detection of these properties, represent the main tool for identification of CSCs. This article summarizes both in vitro and in vivo methods used to identify the CSCs with emphasis on recently employed techniques of CSCs detection. In vivo tumorigenicity assay, sphere formation assay and colony‑ forming unit assay belong to the most commonly used functional assays. Further, label‑ retention assay and aldehyde dehydrogenase activity assay are described in this article.

Key words:
cancer stem cells – functional assays – tumorigenicity – tumor spheres – colony‑ forming unit assay – side population cells – aldehyde dehydrogenase

The study was supported by grant of Internal Grant Agency of the Czech Ministry of Health No. NT13443-4 and by the European Regional Development Fund and the State Budget of the Czech Republic – RECAMO, CZ.1.05//2.1.00/03.0101 and by the project CEB, OP VK CZ.1.07/2.3.00/20.0183.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
16. 1. 2014

Accepted:
4. 4. 2014

Zdroje

1. Clarke MF, Dick JE, Dirks PB et al. Cancer stem cells − perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res 2006; 66(19): 9339– 9344.

2. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012; 21(3): 283– 296. doi: 10.1016/ j.ccr.2012.03.003.

3. Vidal SJ, Rodriguez‑ Bravo V, Galsky M et al. Targeting cancer stem cells to suppress acquired chemotherapy resistance. Oncogene 2013; 10: 1−13. doi: 10.1038/ onc.2013.411.

4. Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 2008; 8(7): 545– 554. doi: 10.1038/ nrc2419.

5. Hittelman WN, Liao Y, Wang L et al. Are cancer stem cells radioresistant? Future Oncol 2010; 6(10): 1563– 1576. doi: 10.2217/ fon.10.121.

6. Cogle CR. Cancer stem cells: historical perspectives and lessons from leukemia. In: Alison AL (ed.). Cancer stem cells in solid tumors. Springer 2011: 3– 11.

7. Welte Y, Adjaye J, Lehrach HR et al. Cancer stem cells in solid tumors: elusive or illusive? Cell Commun Signal 2010; 8(1): 6. doi: 10.1186/ 1478- 811X‑ 8- 6.

8. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3(7): 730– 737.

9. Al‑ Hajj M, Wicha MS, Benito‑ Hernandez A et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983– 3988.

10. Beck B, Blanpain C. Unravelling cancer stem cell potential. Nat Rev Cancer 2013; 13(10): 727– 738. doi: 10.1038/ nrc3597.

11. Singh SK, Hawkins C, Clarke ID et al. Identification of human brain tumour initiating cells. Nature 2004; 432(7015): 396– 401.

12. Walter D, Satheesha S, Albrecht P et al. CD133 positive embryonal rhabdomyosarcoma stem‑like cell population is enriched in rhabdospheres. PLoS One 2011; 6(5): e19506. doi: 10.1371/ journal.pone.0019506.

13. Hemmati HD, Nakano I, Lazareff JA et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003; 100(25): 15178– 15183.

14. Ponti D, Costa A, Zaffaroni N et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/ progenitor cell properties. Cancer Res 2005; 65(13): 5506– 5011.

15. McDermott SP, Eppert K, Lechman ER et al. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood 2010; 116(2): 193– 200. doi: 10.1182/ blood‑ 2010- 02- 271841.

16. Quintana E, Shackleton M, Sabel MS et al. Efficient tumour formation by single human melanoma cells. Nature 2008; 456(7222): 593– 598. doi: 10.1038/ nature07567.

17. Agliano A, Martin‑Padura I, Mancuso P et al. Human acute leukemia cells injected in NOD/ LtSz‑ scid/ IL‑2Rgamma null mice generate a faster and more efficient disease compared to other NOD/ scid‑related strains. Int J Cancer 2008; 123(9): 2222– 2227. doi: 10.1002/ ijc.23772.

18. Ishizawa K, Rasheed ZA, Karisch R et al. Tumor‑ initiating cells are rare in many human tumors. Cell Stem Cell 2010; 7(3): 279– 282. doi: 10.1016/ j.stem.2010.08.009.

19. Scadden DT. The stem‑ cell niche as an entity of action. Nature 2006; 441: 1075– 1079.

20. Orimo A, Gupta PB, Sgroi DC et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF‑ 1/ CXCL12 secretion. Cell 2005; 121(3): 335– 348.

21. Olumi AF, Grossfeld GD, Hayward SW et al. Carcinoma‑associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 1999; 59(19): 5002– 5011.

22. Tzukerman M, Skorecki K. A novel experimental platform for investigating tumorigenesis and anti‑cancer therapy in a human microenvironment derived from embryonic stem cells. Discov Med 2003, 3(19): 51– 54.

23. Micke P, Ostman A. Tumour‑ stroma interaction: cancer‑associated fibroblasts as novel targets in anti‑cancer therapy? Lung Cancer 2004; 45 (Suppl 2): 163– 175.

24. Fabris VT, Sahores A, Vanzulli SI et al. Inoculated mammary carcinoma‑associated fibroblasts: contribution to hormone independent tumor growth. BMC Cancer 2010; 10: 293. doi: 10.1186/ 1471- 2407- 10- 293.

25. Yeung TM, Gandhi SC, Wilding JL et al. Cancer stem cells from colorectal cancer‑ derived cell lines. Proc Natl Acad Sci USA 2010; 107(8): 3722– 3727. doi: 10.1073/ pnas.0915135107.

26. Di Fiore R, Guercio A, Puleio R et al. Modeling human osteosarcoma in mice through 3AB‑ OS cancer stem cell xenografts. J Cell Biochem 2012; 113(11): 3380– 3392. doi: 10.1002/ jcb.24214.

27. Wyckoff J, Gligorijevic B, Entenberg D et al. High‑resolution multiphoton imaging of tumors in vivo. Cold Spring Harb Protoc 2011; 2011(10): 1167– 1184. doi: 10.1101/ pdb.top065904.

28. Chen J, Li Y, Yu TS et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012; 488(7412): 522– 526. doi: 10.1038/ nature11287.

29. Driessens G, Beck B, Caauwe A et al. Defining the mode of tumour growth by clonal analysis. Nature 2012; 488(7412): 527– 530. doi: 10.1038/ nature11344.

30. Zomer A, Ellenbroek SI, Ritsma L et al. Intravital imaging of cancer stem cell plasticity in mammary tumors. Stem Cells 2013; 31(3): 602– 606. doi: 10.1002/ stem.1296.

31. Lathia JD, Gallagher J, Myers JT et al. Direct in vivo evidence for tumor propagation by glioblastoma cancer stem cells. PLoS One 2011; 6(9): e24807. doi: 10.1371/ journal.pone.0024807.

32. Alison MR, Lim SM, Nicholson LJ. Cancer stem cells: problems for therapy? J Pathol 2011; 223(2): 147– 161. doi: 10.1002/ path.2793.

33. Shaw FL, Harrison H, Spence K et al. A detailed mammosphere assay protocol for the quantification of breast stem cell activity. J Mammary Gland Biol Neoplasia 2012; 17(2): 111– 117. doi: 10.1007/ s10911- 012- 9255- 3.

34. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992; 255(5052): 1707– 1710.

35. Dontu G, Wicha MS. Survival of mammary stem cells in suspension culture: implications for stem cell biology and neoplasia. J Mammary Gland Biol Neoplasia 2005; 10(1): 75– 86.

36. Singh SK, Clarke ID, Terasaki M et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63(18): 5821– 5828.

37. Tirino V, Desiderio V, d‘Aquino R et al. Detection and characterization of CD133+ cancer stem cells in human solid tumours. PLoS One 2008; 3(10): e3469. doi: 10.1371/ journal.pone.0003469.

38. Di Fiore R, Santulli A, Ferrante R et al. Identification and expansion of human osteosarcoma‑ cancer‑ stem cells by long‑term 3-aminobenzamide treatment. J Cell Physiol 2009; 219(2): 301– 313. doi: 10.1002/ /jcp.21667.

39. Kanwar SS, Yu Y, Nautiyal J et al. The Wnt/ beta‑catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer 2010; 9: 212. doi: 10.1186/ 1476- 4598- 9- 212.

40. Lee EK, Cho H, Kim CW. Proteomic analysis of cancer stem cells in human prostate cancer cells. Biochem Biophys Res Commun 2011; 412(2): 279– 285. doi: 10.1016/ j.bbrc.2011.07.083.

41. Cao L, Zhou Y, Zhai B et al. Sphere‑forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol 2011; 11: 71. doi: 10.1186/ 1471- 230X‑ 11- 71.

42. Ye J, Wu D, Shen J et al. Enrichment of colorectal cancer stem cells through epithelial‑ mesenchymal transition via CDH1 knockdown. Mol Med Rep 2012; 6(3): 507– 512. doi: 10.3892/ mmr.2012.938.

43. Yang M, Yan M, Zhang R et al. Side population cells isolated from human osteosarcoma are enriched with tumor‑ initiating cells. Cancer Sci 2011; 102(10): 1774– 1781. doi: 10.1111/ j.1349- 7006.2011.02028.x.

44. Fedr R, Pernicová Z, Slabáková E et al. Automatic cell cloning assay for determining the clonogenic capacity of cancer and cancer stem‑like cells. Cytometry A 2013; 83(5): 472– 482. doi: 10.1002/ cyto.a.22273.

45. Wylie PG, Bowen WP. Determination of cell colony formation in a high‑content screening assay. Clin Lab Med 2007; 27(1): 193– 199.

46. Bunting KD. ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 2002; 20(1): 11– 20.

47. Dean M. ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 2009; 14(1): 3– 9. doi: 10.1007/ s10911- 009- 9109- 9.

48. Veselska R, Skoda J, Neradil J. Detection of cancer stem cell markers in sarcomas. Klin Onkol 2012; 25 (Suppl 2): 2S16– 2S20.

49. Mayol JF, Loeuillet C, Hérodin F et al. Characterisation of normal and cancer stem cells: one experimental paradigm for two kinds of stem cells. Bioessays 2009; 31(9): 993– 1001. doi: 10.1002/ bies.200900041.

50. Hiraga T, Ito S, Nakamura H. Side population in MDA‑ MB‑ 231 human breast cancer cells exhibits cancer stem cell‑like properties without higher bone‑ metastatic potential. Oncol Rep 2011; 25(1): 289– 296.

51. Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem‑like cells that self‑ renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008; 10(2): R25. doi: 10.1186/ bcr1982.

52. Dembinski JL, Krauss S. Characterization and functional analysis of a slow cycling stem cell‑like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis 2009; 26(7): 611– 623. doi: 10.1007/ s10585- 009- 9260- 0.

53. Roesch A, Fukunaga‑ Kalabis M, Schmidt EC et al. A temporarily distinct subpopulation of slow‑ cycling melanoma cells is required for continuous tumor growth. Cell 2010; 141(4): 583– 594. doi: 10.1016/ j.cell.2010.04.020.

54. McDonald SA, Graham TA, Schier S et al. Stem cells and solid cancers. Virchows Arch 2009; 455(1): 1– 13. doi: 10.1007/ s00428- 009- 0783- 1.

55. Lee JT, Herlyn M. Old disease, new culprit: tumor stem cells in cancer. J Cell Physiol 2007; 213(3): 603– 609.

56. Deleyrolle LP, Harding A, Cato K et al. Evidence for label‑ retaining tumour‑ initiating cells in human glioblastoma. Brain 2011; 134(Pt 5): 1331– 1343. doi: 10.1093/ brain/ awr081.

57. Willan PM, Farnie G. Application of stem cell assays for the characterization of cancer stem cells. In: Allan AL (ed.). Cancer stem cells in solid tumors. Springer 2011: 259−282.

58. Alison MR, Murphy G, Leedham S. Stem cells and cancer: a deadly mix. Cell Tissue Res 2008; 331(1): 109– 124.

59. Storms RW, Trujillo AP, Springer JB et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci USA 1999; 96(16): 9118– 9123.