Cancer Stem Cells: Proteomic Approaches for New Potential Diagnostic and Prognostic Biomarkers

  • Patrizia Bottoni
  • Bruno Giardina
  • Roberto Scatena
Chapter
First Online:

Abstract

The recent identification of cells with stem cell-like behaviour in several types of human cancers has opened new avenues for a better understanding of molecular mechanisms and intracellular signalling events that drive a complex degenerative process such as carcinogenesis. The investigation of the pathophysiology of CSC represents an interesting subject for proteomic analysis that in last decade has exploded with thousands of experimental and clinical studies examining various aspects of oncology. Proteomic approaches have produced a wealth of data identifying proteins that regulate self-renewal, pluripotency and differentiation of stem cells, even though with all the limits related to protocol variability that renders rather difficult to create a definitive proteome profile. More recently, several studies directly examining CSCs proteome or showing in cancer cell proteome altered expression levels of proteins that are actually considered characteristic of stemness have been published. The possibility of applying proteomic strategies to the study of CSCs and of the complex series of molecular interactions and phosphorylation events that occur at the level of protein components of the signalling pathways involved in self-renewal and carcinogenesis could shed new light on the molecular mechanisms that form the basis of this process, with all potential clinical applications related to the physiopathology of CSCs.

Keywords

Cell Surface Marker hESC Line Glioblastoma Stem Cell Ovarian Cancer Cell Line SKOV3 Colon CSCs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Ahn SM, Goode RJ, Simpson RJ (2008a) Stem cell markers: insights from membrane proteomics? Proteomics. 8:4946–57.PubMedCrossRefGoogle Scholar
  2. Ahn Y, Hwang CY, Lee SR et al (2008b) The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4. Biochem J. 412:331–8.PubMedCrossRefGoogle Scholar
  3. Al-Hajj M, Wicha MS, Benito-Hernandez A et al (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–8.PubMedCrossRefGoogle Scholar
  4. Baharvand H, Fathi A, van Hoof D, Salekdeh GH (2007) Concise review: trends in stem cell proteomics. Stem Cells 25:1888–903.PubMedCrossRefGoogle Scholar
  5. Baharvand H, Hajheidari M, Ashtiani SK, Salekdeh GH (2006) Proteomic signature of human embryonic stem cells. Proteomics 6:3544–9.PubMedCrossRefGoogle Scholar
  6. Baumann M, Krause M, Hill R (2008) Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 8:545–54.PubMedCrossRefGoogle Scholar
  7. Beachy PA, Karhadkar SS, Berman DM (2004) Tissue repair and stem cell renewal in carcinogenesis. Nature 432:324–31.PubMedCrossRefGoogle Scholar
  8. Bendall SC, Hughes C, Campbell JL et al (2009) An enhanced mass spectrometry approach reveals human embryonic stem cell growth factors in culture. Mol Cell Proteomics 8:421–32.PubMedCrossRefGoogle Scholar
  9. Bendall SC, Stewart MH, Menendez P et al (2007) IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature 448:1015–21.PubMedCrossRefGoogle Scholar
  10. Bonnet D and Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–7.PubMedCrossRefGoogle Scholar
  11. Brennan C, Momota H, Hambardzumyan D et al (2009) Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS One 4:e7752.PubMedCrossRefGoogle Scholar
  12. Brimble SN, Zeng X, Weiler DA, et al (2004) Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001. Stem Cells Dev. 13:585–97.PubMedCrossRefGoogle Scholar
  13. Bromberg J (2002) Stat proteins and oncogenesis. J Clin Invest 109:1139–1142.PubMedGoogle Scholar
  14. Chaerkady R, Kerr CL, Kandasamy K et al (2010) Comparative proteomics of human embryonic stem cells and embryonal carcinoma cells. Proteomics 10:1359–73.PubMedCrossRefGoogle Scholar
  15. Chaerkady R, Kerr CL, Marimuthu A et al (2009) Temporal analysis of neural differentiation using quantitative proteomics. J Proteome Res. 8:1315–26.PubMedCrossRefGoogle Scholar
  16. Christofk HR, Vander Heiden MG, Wu N et al (2008) Pyruvate kinase M2 is a phosphotyrosine binding protein. Nature 452:181–186.PubMedCrossRefGoogle Scholar
  17. Chung JY, Hong SM, Choi BY et al (2009) The expression of phospho-AKT, phospho-mTOR, and PTEN in extrahepatic cholangiocarcinoma. Clin Cancer Res. 15:660–7.PubMedCrossRefGoogle Scholar
  18. Collier TS, Sarkar P, Rao B, Muddiman DC (2010) Quantitative top-down proteomics of SILAC labeled human embryonic stem cells. J Am Soc Mass Spectrom. 21:879–89.PubMedCrossRefGoogle Scholar
  19. Dai Z, Yin J, He H et al (2010) Mitochondrial comparative proteomics of human ovarian cancer cells and their platinum-resistant sublines. Proteomics 10:3789–99.PubMedCrossRefGoogle Scholar
  20. Dalerba P, Dylla SJ, Park IK, et al (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104:10158–63.PubMedCrossRefGoogle Scholar
  21. Dormeyer W, van Hoof D, Braam SR et al (2008a) Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells. J Proteome Res. 7:2936–51.PubMedCrossRefGoogle Scholar
  22. Dormeyer W, van Hoof D, Mummery CL et al (2008b) A practical guide for the identification of membrane and plasma membrane proteins in human embryonic stem cells and human embryonal carcinoma cells. Proteomics 8:4036–53.PubMedCrossRefGoogle Scholar
  23. 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 102:1265–75.PubMedCrossRefGoogle Scholar
  24. Fathi A, Pakzad M, Taei A et al (2009) Comparative proteome and transcriptome analyses of embryonic stem cells during embryoid body-based differentiation. Proteomics 9:4859–70.PubMedCrossRefGoogle Scholar
  25. Foss EJ, Radulovic D, Shaffer SA et al (2007) Genetic basis of proteome variation in yeast. Nat Genet. 39:1369–75.PubMedCrossRefGoogle Scholar
  26. Foster LJ, Zeemann PA, Li C et al (2005) Differential expression profiling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation. Stem Cells 23:1367–77.PubMedCrossRefGoogle Scholar
  27. Harkness L, Christiansen H, Nehlin J et al (2008) Identification of a membrane proteomic signature for human embryonic stem cells independent of culture conditions. Stem Cell Res 1:219–27.PubMedCrossRefGoogle Scholar
  28. Heimberger AB, Priebe W (2008) Small molecular inhibitors of p-STAT3: novel agents for treatment of primary and metastatic CNS cancers. Recent Pat CNS Drug Discov. 3:179–88.PubMedCrossRefGoogle Scholar
  29. Hemler ME (2005) Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 10:801–811.CrossRefGoogle Scholar
  30. Hoffrogge R, Mikkat S, Scharf C et al (2006) 2-DE proteome analysis of a proliferating and differentiating human neuronal stem cell line (ReNcell VM). Proteomics 6:1833–47.PubMedCrossRefGoogle Scholar
  31. Huang SM, Mishina YM, Liu S et al (2009) Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461:614–20.PubMedCrossRefGoogle Scholar
  32. Keenan J, Murphy L, Henry M et al (2009) Proteomic analysis of multidrug-resistance mechanisms in adriamycin-resistant variants of DLKP, a squamous lung cancer cell line. Proteomics 9:1556–66.PubMedCrossRefGoogle Scholar
  33. Krijgsveld J, Whetton AD, Lee B et al (2008) Proteome biology of stem cells: a new joint HUPO and ISSCR initiative. Mol Cell Proteomics 7:204–5.PubMedGoogle Scholar
  34. Le Naour F, André M, Greco C et al (2006) Profiling of the tetraspanin web of human colon cancer cells. Mol Cell Proteomics 5:845–57.PubMedCrossRefGoogle Scholar
  35. Lee DH, Chung K, Song JA et al (2010a) Proteomic identification of paclitaxel-resistance associated hnRNP A2 and GDI 2 proteins in human ovarian cancer cells. J Proteome Res. 9:5668–76.PubMedCrossRefGoogle Scholar
  36. Lee EK, Han GY, Park HW et al (2010b) Transgelin promotes migration and invasion of cancer stem cells. J Proteome Res. 9:5108–17.PubMedCrossRefGoogle Scholar
  37. Lee WJ, Kim DU, Lee MY, Choi KY (2007) Identification of proteins interacting with the catalytic subunit of PP2A by proteomics. Proteomics 7:206–14.PubMedCrossRefGoogle Scholar
  38. Lerou PH and Daley GQ (2005) Therapeutic potential of embryonic stem cells. Blood Rev. 19:321–31.PubMedCrossRefGoogle Scholar
  39. Leslie K, Lang C, Devgan G et al (2006) Cyclin D1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3. Cancer Res 66:2544–2552.PubMedCrossRefGoogle Scholar
  40. Levy DE, Darnell JE Jr. (2002) Stats: Transcriptional control and biological impact. Nat Rev Mol Cell Biol 3:651–662.PubMedCrossRefGoogle Scholar
  41. Li C, Heidt DG, Dalerba P et al (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–7.PubMedCrossRefGoogle Scholar
  42. Lim JW and Bodnar A (2002) Proteome analysis of conditioned medium from mouse embryonic fibroblast feeder layers which support the growth of human embryonic stem cells. Proteomics 2: 1187–203.PubMedCrossRefGoogle Scholar
  43. Lottaz C, Beier D, Meyer K et al (2010) Transcriptional profiles of CD133+ and CD133- glioblastoma-derived cancer stem cell lines suggest different cells of origin. Cancer Res. 70:2030–40.PubMedCrossRefGoogle Scholar
  44. Ma S, Chan KW, Lee TK et al (2008) Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res. 6:1146–53.PubMedCrossRefGoogle Scholar
  45. Madoz-Gurpide J, Canamero M, Sanchez L et al (2007) A proteomics analysis of cell signaling alterations in colorectal cancer. Mol Cell Proteomics 6:2150–64.PubMedCrossRefGoogle Scholar
  46. Mahmoudi T, Li VS, Ng SS et al (2009) The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 28:3329–40.PubMedCrossRefGoogle Scholar
  47. Nagano K, Taoka M, Yamauchi Y et al (2005) Large-scale identification of proteins expressed in mouse embryonic stem cells. Proteomics 5:1346–61.PubMedCrossRefGoogle Scholar
  48. Nilsson CL, Dillon R, Devakumar A et al (2010) Quantitative phosphoproteomic analysis of the STAT3/IL-6/HIF1alpha signalling network: an initial study in GSC11 glioblastoma stem cells. J Proteome Res. 9:430–43.PubMedCrossRefGoogle Scholar
  49. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–10.PubMedCrossRefGoogle Scholar
  50. Patrawala L, Calhoun T, Schneider-Broussard R et al (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–708.PubMedCrossRefGoogle Scholar
  51. Prokhorova TA, Rigbolt KT, Johansen PT et al (2009) Stable isotope labeling by amino acids in cell culture (SILAC) and quantitative comparison of the membrane proteomes of self-renewing and differentiating human embryonic stem cells. Mol Cell Proteomics 8:959–70.PubMedCrossRefGoogle Scholar
  52. Prowse AB, McQuade LR, Bryant KJ et al (2007) Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media. J Proteome Res. 6:3796–807.PubMedCrossRefGoogle Scholar
  53. Qumsiyeh MB, Li P (2001) Molecular biology of cancer: Cytogenetics. In: De Vita VT, Hellmann S, Rosenberg SA (eds) Cancer: Principles and Practice of Oncology, 6th edn. JB Lippincott Company, Philadelphia, pp. 77–90.Google Scholar
  54. Ricci-Vitiani L, Collinari C, di Martino S et al (2010) Thymosin {beta}4 targeting impairs tumorigenic activity of colon cancer stem cells. FASEB J 24:4291–301.PubMedCrossRefGoogle Scholar
  55. Scatena R, Bottoni P, Giardina B (2008) Modulation of cancer cell line differentiation: a neglected proteomic analysis with potential implications in pathophysiology, diagnosis, prognosis, and therapy of cancer. Proteomics Clin. Appl. 2:229–237.PubMedCrossRefGoogle Scholar
  56. Scatena R, Bottoni P, Pontoglio A, Giardina B (2010) Revisiting the Warburg effect in cancer cells with proteomics. The emergence of new approaches to diagnosis, prognosis and therapy. Proteomics Clin Appl 4:143–158.PubMedCrossRefGoogle Scholar
  57. Seliger B (2008) Molecular mechanisms of MHC class I abnormalities and APM components in human tumors. Cancer Immunol Immunother. 57:1719–26.PubMedCrossRefGoogle Scholar
  58. Sherry MM, Reeves A, Wu JK, Cochran BH (2009) STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells 27:2383–92.PubMedCrossRefGoogle Scholar
  59. Singh SK, Hawkins C, Clarke ID, et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401.PubMedCrossRefGoogle Scholar
  60. Skvortsova I, Skvortsov S, Stasyk T et al (2008) Intracellular signaling pathways regulating radioresistance of human prostate carcinoma cells. Proteomics 8:4521–33.PubMedCrossRefGoogle Scholar
  61. Sperger JM, Chen X, Draper JS et al (2003) Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci USA 100:13350–55.PubMedCrossRefGoogle Scholar
  62. Spooncer E, Brouard N, Nilsson SK, et al (2008) Developmental fate determination and marker discovery in hematopoietic stem cell biology using proteomic fingerprinting. Mol Cell Proteomics 7:573–81.PubMedGoogle Scholar
  63. Steiniger SC, Coppinger JA, Krüger JA et al (2008) Quantitative mass spectrometry identifies drug targets in cancer stem cell-containing side population. Stem Cells 26:3037–46.PubMedCrossRefGoogle Scholar
  64. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A et al (2008) An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 68:6084–91.PubMedCrossRefGoogle Scholar
  65. Unlu M, Morgan ME, Minden JS (1997) Difference gel electrophoresis: A single gel method for detecting changes in protein extracts. Electrophoresis 18:2071–2077.PubMedCrossRefGoogle Scholar
  66. Unwin RD, Smith DL, Blinco D et al (2006) Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells. Blood. 107:4687–94.PubMedCrossRefGoogle Scholar
  67. Van Hoof D, Dormeyer W, Braam SR et al (2010) Identification of cell surface proteins for antibody-based selection of human embryonic stem cell-derived cardiomyocytes. J Proteome Res. 9:1610–8.PubMedCrossRefGoogle Scholar
  68. Van Hoof D, Passier R, Ward-Van Oostwaard D et al (2006) A quest for human and mouse embryonic stem cell-specific proteins. Mol Cell Proteomics. 5:1261–73.PubMedCrossRefGoogle Scholar
  69. Wang J, Wakeman TP, Lathia JD et al (2010) Notch promotes radioresistance of glioma stem cells. Stem Cells 28:17–28.PubMedCrossRefGoogle Scholar
  70. Wang Z, Li Y, Banerjee S et al. Emerging role of Notch in stem cells and cancer. Cancer Lett 2009, 279:8–12.PubMedCrossRefGoogle Scholar
  71. Whetton AD, Williamson AJ, Krijgsveld J et al (2008) The time is right: proteome biology of stem cells. Cell Stem Cell. 2:215–7.PubMedCrossRefGoogle Scholar
  72. Wiederschain D, Chen L, Johnson B et al (2007) Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis. Mol Cell Biol. 27:4968–79.PubMedCrossRefGoogle Scholar
  73. Yang ZF, Ngai P, Ho DW, et al (2008) Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 47:919–28.PubMedCrossRefGoogle Scholar
  74. Zhou C, Nitschke AM, Xiong W et al (2008) Proteomic analysis of tumor necrosis factor-alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype. Breast Cancer Res. 10:R105.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Patrizia Bottoni
    • 1
  • Bruno Giardina
    • 1
  • Roberto Scatena
    • 1
  1. 1.Department of Laboratory MedicineCatholic UniversityRomeItaly

Personalised recommendations