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Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications

  • Current Concepts in Clinical Surgery
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Since the discovery of cancer cells with stem-like characteristics in hematopoietic malignancies and, more recently, in solid tumors, enormous attention has been paid to the stem-cell nature of pancreatic cancer. Among the most important properties of cancer stem cells their high capacity for tumorigenicity as well as their ability to metastasize is under special research interest today.

Methods

Here, we give a brief overview of main components used to confirm the stem-cell-like behavior of putative cancer stem cells and discuss markers and methods for identifying them in pancreatic cancer. Finally, the review provides some new suggestions as to how specifically target these cells and improve current therapy regimens.

Results

The cancer stem-cell hypothesis is a fundamentally different model of carcinogenesis composed of two separate but dependent on each other characteristics of stem cells—aberrant activation of their tightly regulated processes of self-renewal and differentiation and their resistance towards chemo- and radiotherapy. The cancer stem cells may further be identified based on their expression of cell surface markers or their functional characteristics. The concept of molecular targeting of such highly tumorigenic cancer cells aimed to sensitize tumors toward conventional therapies and effectively abrogate tumor growth and metastasis.

Conclusions

The presence of cancer stem cells in pancreatic tumors has prognostic relevance and influences therapeutic response. Evidence suggests that metastatic potential may be conferred to these highly tumorigenic cells as well. A better understanding of the biological behavior of these cells may further improve therapeutic approaches and outcomes in patients with this devastating disease.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics. CA Cancer J Clin 58(2):71–96. doi:10.3322/CA.2007.0010

    Article  PubMed  Google Scholar 

  2. Griffin JF, Smalley SR, Jewell W, Paradelo JC, Reymond RD, Hassanein RE, Evans RG (1990) Patterns of failure after curative resection of pancreatic carcinoma. Cancer 1:56–61

    Article  Google Scholar 

  3. Niederhuber JE, Brennan MF, Menck HR (1995) The National Cancer Data Base report on pancreatic cancer. Cancer 76(9):1671–1677

    Article  CAS  PubMed  Google Scholar 

  4. Rosewicz S, Wiedenmann B (1997) Pancreatic carcinoma. Lancet 349:485–489. doi:10.1016/S0140-6736(96)05523-7

    Article  CAS  PubMed  Google Scholar 

  5. Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA (2006) Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev 20(10):1218–1249

    Article  CAS  PubMed  Google Scholar 

  6. Logsdon CD, Simeone DM, Binkley C, Arumugam T, Greenson JK, Giordano TJ, Misek DE, Kuick R, Hanash S (2003) Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 63(10):2649–2657

    CAS  PubMed  Google Scholar 

  7. Bardeesy N, DePinho RA (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2(12):897–909

    Article  CAS  PubMed  Google Scholar 

  8. Al-Hajj M, Clarke MF (2004) Self-renewal and solid tumor stem cells. Oncogene 23(43):7274–7282

    Article  CAS  PubMed  Google Scholar 

  9. Leach SD (2005) Epithelial differentiation in pancreatic development and neoplasia: new niches for nestin and Notch. J Clin Gastroenterol 39(4 Suppl 2):S78–82

    Article  PubMed  Google Scholar 

  10. Miyamoto Y, Maitra A, Ghosh B, Zechner U, Argani P, Iacobuzio-Donahue CA, Sriuranpong V, Iso T, Meszoely IM, Wolfe MS, Hruban RH, Ball DW, Schmid RM, Leach SD (2003) Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell 3(6):565–576

    Article  CAS  PubMed  Google Scholar 

  11. Zeng G, Germinaro M, Micsenyi A, Monga NK, Bell A, Sood A, Malhotra V, Sood N, Midda V, Monga DK, Kokkinakis DM, Monga SP (2006) Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma. Neoplasia 8(4):279–289

    Article  CAS  PubMed  Google Scholar 

  12. Pasca di Magliano M, Biankin AV, Heiser PW, Cano DA, Gutierrez PJ, Deramaudt T, Segara D, Dawson AC, Kench JG, Henshall SM, Sutherland RL, Dlugosz A, Rustgi AK, Hebrok M (2007) Common activation of canonical Wnt signaling in pancreatic adenocarcinoma. PLoS ONE 2(11):e1155

    Article  PubMed  CAS  Google Scholar 

  13. Kayed H, Kleeff J, Keleg S, Guo J, Ketterer K, Berberat PO, Giese N, Esposito I, Giese T, Büchler MW, Friess H (2004) Indian hedgehog signaling pathway: expression and regulation in pancreatic cancer. Int J Cancer 110(5):668–676

    Article  CAS  PubMed  Google Scholar 

  14. Tian H, Callahan CA, Dupree KJ, Darbonne WC, Ahn CP, Scales SJ, de Sauvage FJ (2009) Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci U S A 106(11):4254–4259

    Article  CAS  PubMed  Google Scholar 

  15. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernández-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M (2003) Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425(6960):851–856

    Article  CAS  PubMed  Google Scholar 

  16. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037

    Article  CAS  PubMed  Google Scholar 

  17. Lee CJ, Dosch J, Simeone DM (2008) Pancreatic cancer stem cells. J Clin Oncol 26(17):2806–2812

    Article  PubMed  Google Scholar 

  18. Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275–284

    Article  CAS  PubMed  Google Scholar 

  19. Tang C, Ang BT, Pervaiz S (2007) Cancer stem cell: target for anti-cancer therapy. FASEB J 21(14):3777–3785

    Article  CAS  PubMed  Google Scholar 

  20. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323

    Article  CAS  PubMed  Google Scholar 

  21. Zhou J, Wang CY, Liu T, Wu B, Zhou F, Xiong JX, Wu HS, Tao J, Zhao G, Yang M, Gou SM (2008) Persistence of side population cells with high drug efflux capacity in pancreatic cancer. World J Gastroenterol 14(6):925–930

    Article  CAS  PubMed  Google Scholar 

  22. Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE (2007) Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 14(12):3629–3637

    Article  PubMed  Google Scholar 

  23. Asanuma K, Moriai R, Yajima T, Yagihashi A, Yamada M, Kobayashi D, Watanabe N (2000) Survivin as a radioresistance factor in pancreatic cancer. Jpn J Cancer Res 91(11):1204–1209

    CAS  PubMed  Google Scholar 

  24. Ayyanan A, Civenni G, Ciarloni L, Morel C, Mueller N, Lefort K, Mandinova A, Raffoul W, Fiche M, Dotto GP, Brisken C (2006) Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc Natl Acad Sci U S A 103(10):3799–3804

    Article  CAS  PubMed  Google Scholar 

  25. Phillips TM, McBride WH, Pajonk F (2006) The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 98(24):1777–1785

    PubMed  Google Scholar 

  26. Mungamuri SK, Yang X, Thor AD, Somasundaram K (2006) Survival signaling by Notch1: mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Res 66(9):4715–4724

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100(7):3983–3988

    Article  CAS  PubMed  Google Scholar 

  29. Shmelkov SV, St Clair R, Lyden D, Rafii S (2005) AC133/CD133/Prominin-1. Int J Biochem Cell Biol 37(4):715–719

    Article  CAS  PubMed  Google Scholar 

  30. Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ (1999) In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia 1(1):50–62

    Article  CAS  PubMed  Google Scholar 

  31. Miller RJ, Banisadr G, Bhattacharyya BJ (2008) CXCR4 signaling in the regulation of stem cell migration and development. J Neuroimmunol 198(1–2):31–38

    Article  CAS  PubMed  Google Scholar 

  32. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715

    Article  CAS  PubMed  Google Scholar 

  33. Maeda S, Shinchi H, Kurahara H, Mataki Y, Maemura K, Sato M, Natsugoe S, Aikou T, Takao S (2008) CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer. Br J Cancer 98(8):1389–1397

    Article  CAS  PubMed  Google Scholar 

  34. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D'Angelica M, Kemeny N, Lyden D, Rafii S (2008) CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest 118(6):2111–2120

    CAS  PubMed  Google Scholar 

  35. Olempska M, Eisenach PA, Ammerpohl O, Ungefroren H, Fandrich F, Kalthoff H (2007) Detection of tumor stem-cell markers in pancreatic carcinoma cell lines. Hepatobiliary Pancreat Dis Int 6(1):92–97

    CAS  PubMed  Google Scholar 

  36. Polgar O, Robey RW, Bates SE (2008) ABCG2: structure, function and role in drug response. Expert Opin Drug Metab Toxicol 4(1):1–15

    Article  CAS  PubMed  Google Scholar 

  37. Hadnagy A, Gaboury L, Beaulieu R, Balicki D (2006) SP analysis may be used to identify cancer stem cell populations. Exp Cell Res 312(19):3701–3710

    Article  CAS  PubMed  Google Scholar 

  38. 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(14):6207–6219

    Article  CAS  PubMed  Google Scholar 

  39. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM (2006) Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344

    Article  CAS  PubMed  Google Scholar 

  40. Ma S, Chan KW, Guan XY (2008) In search of liver cancer stem cells. Stem Cell Rev 4(3):179–192

    Article  CAS  PubMed  Google Scholar 

  41. Stanger BZ, Stiles B, Lauwers GY, Bardeesy N, Mendoza M, Wang Y, Greenwood A, Cheng KH, McLaughlin M, Brown D, Depinho RA, Wu H, Melton DA, Dor Y (2005) Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 8(3):185–195

    Article  CAS  PubMed  Google Scholar 

  42. Maitra A, Hruban RH (2008) Pancreatic cancer. Annu Rev Pathol 3:157–188. doi:10.1146/annurev.pathmechdis.3.121806.154305

    Article  CAS  PubMed  Google Scholar 

  43. Ischenko I, Camaj P, Seeliger H, Kleespies A, Guba M, De Toni EN, Schwarz B, Graeb C, Eichhorn ME, Jauch KW, Bruns CJ (2008) Inhibition of Src tyrosine kinase reverts chemoresistance toward 5-fluorouracil in human pancreatic carcinoma cells: an involvement of epidermal growth factor receptor signaling. Oncogene 27(57):7212–7222

    Article  CAS  PubMed  Google Scholar 

  44. Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE (2004) RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine. Oncogene 23(8):1539–1548

    Article  CAS  PubMed  Google Scholar 

  45. 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(10):4827–4833

    Article  CAS  PubMed  Google Scholar 

  46. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760

    Article  CAS  PubMed  Google Scholar 

  47. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY (2008) CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 27(12):1749–1758

    Article  CAS  PubMed  Google Scholar 

  48. Ischenko I, Seeliger H, Schaffer M, Jauch KW, Bruns CJ (2008) Cancer stem cells: how can we target them? Curr Med Chem 15(30):3171–3184. doi:10.2174/092986708786848541

    Article  CAS  PubMed  Google Scholar 

  49. James LF, Panter KE, Gaffield W, Molyneux RJ (2004) Biomedical applications of poisonous plant research. J Agric Food Chem 52(11):3211–3230

    Article  CAS  PubMed  Google Scholar 

  50. Chen X, Horiuchi A, Kikuchi N, Osada R, Yoshida J, Shiozawa T, Konishi I (2007) Hedgehog signal pathway is activated in ovarian carcinomas, correlating with cell proliferation: it's inhibition leads to growth suppression and apoptosis. Cancer Sci 98(1):68–76

    Article  CAS  PubMed  Google Scholar 

  51. Chen JK, Taipale J, Cooper MK, Beachy PA (2002) Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16(21):2743–2748

    Article  CAS  PubMed  Google Scholar 

  52. Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, Karikari C, Alvarez H, Iacobuzio-Donahue C, Jimeno A, Gabrielson KL, Matsui W, Maitra A (2007) Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 67(5):2187–2196

    Article  CAS  PubMed  Google Scholar 

  53. Mimeault M, Moore E, Moniaux N, Hénichart JP, Depreux P, Lin MF, Batra SK (2006) Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells. Int J Cancer 118(4):1022–1031

    Article  CAS  PubMed  Google Scholar 

  54. Hu WG, Liu T, Xiong JX, Wang CY (2007) Blockade of sonic hedgehog signal pathway enhances antiproliferative effect of EGFR inhibitor in pancreatic cancer cells. Acta Pharmacol Sin 28(8):1224–1230

    Article  CAS  PubMed  Google Scholar 

  55. Shafaee Z, Schmidt H, Du W, Posner M, Weichselbaum R (2006) Cyclopamine increases the cytotoxic effects of paclitaxel and radiation but not cisplatin and gemcitabine in Hedgehog expressing pancreatic cancer cells. Cancer Chemother Pharmacol 58(6):765–770

    Article  CAS  PubMed  Google Scholar 

  56. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17(2):165–172

    Article  CAS  PubMed  Google Scholar 

  57. Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, Devereux WL, Rhodes JT, Huff CA, Beachy PA, Watkins DN, Matsui W (2007) Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci U S A 104(10):4048–4053

    Article  CAS  PubMed  Google Scholar 

  58. Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, Eberhart CG (2006) Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 66(15):7445–7452

    Article  CAS  PubMed  Google Scholar 

  59. Murtaugh LC, Stanger BZ, Kwan KM, Melton DA (2003) Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 100(25):14920–14925

    Article  CAS  PubMed  Google Scholar 

  60. Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, Brem H, Olivi A, Dimeco F, Vescovi AL (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444(7120):761–765

    Article  CAS  PubMed  Google Scholar 

  61. Hua H, Zhang YQ, Dabernat S, Kritzik M, Dietz D, Sterling L, Sarvetnick N (2006) BMP4 regulates pancreatic progenitor cell expansion through Id2. J Biol Chem 281(19):13574–13580

    Article  CAS  PubMed  Google Scholar 

  62. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, Morrison SJ (2006) Pten dependence distinguishes haematopoietic stem cells from leukemia-initiating cells. Nature 441(7092):475–482

    Article  CAS  PubMed  Google Scholar 

  63. Di Cristofano A, Pandolfi PP (2000) The multiple roles of PTEN in tumor suppression. Cell 100(4):387–390

    Article  PubMed  Google Scholar 

  64. Seeliger H, Guba M, Kleespies A, Jauch KW, Bruns CJ (2007) Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev 26(3–4):611–621

    Article  PubMed  Google Scholar 

  65. Moserle L, Indraccolo S, Ghisi M, Frasson C, Fortunato E, Canevari S, Miotti S, Tosello V, Zamarchi R, Corradin A, Minuzzo S, Rossi E, Basso G, Amadori A (2008) The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects. Cancer Res 68(14):5658–5668

    Article  CAS  PubMed  Google Scholar 

  66. Friess H, Guo XZ, Nan BC, Kleeff O, Büchler MW (1999) Growth factors and cytokines in pancreatic carcinogenesis. Ann N Y Acad Sci 880:110–121

    Article  CAS  PubMed  Google Scholar 

  67. Dippold W, Bernhard H, Büschenfelde KH Meyer zum (1997) Chemotherapy in advanced pancreatic cancer. Int J Pancreatol 21(1):39–41

    CAS  PubMed  Google Scholar 

  68. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439(7072):84–88

    Article  CAS  PubMed  Google Scholar 

  69. Ouhtit A, Abd Elmageed ZY, Abdraboh ME, Lioe TF, Raj MH (2007) In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver. Am J Pathol 171(6):2033–2039

    Article  CAS  PubMed  Google Scholar 

  70. Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L (2008) Brca1 breast tumors contain distinct CD44+/CD24- and CD133 + cells with cancer stem cell characteristics. Breast Cancer Res 10(1):R10. doi:10.1186/bcr1855

    Article  PubMed  CAS  Google Scholar 

  71. Kawasaki BT, Mistree T, Hurt EM, Kalathur M, Farrar WL (2007) Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells. Biochem Biophys Res Commun 364(4):778–782

    Article  CAS  PubMed  Google Scholar 

  72. 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(18):5821–5828

    CAS  PubMed  Google Scholar 

  73. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401

    Article  CAS  PubMed  Google Scholar 

  74. Wu A, Oh S, Wiesner SM, Ericson K, Chen L, Hall WA, Champoux PE, Low WC, Ohlfest JR (2008) Persistence of CD133+ cells in human and mouse glioma cell lines: detailed characterization of GL261 glioma cells with cancer stem cell-like properties. Stem Cells Dev 17(1):173–184

    Article  CAS  PubMed  Google Scholar 

  75. Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN, Steindler DA (2005) Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 7(11):967–976

    Article  CAS  PubMed  Google Scholar 

  76. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 104(24):10158–10163

    Article  CAS  PubMed  Google Scholar 

  77. 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(7123):106–110

    Article  PubMed  CAS  Google Scholar 

  78. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115

    Article  CAS  PubMed  Google Scholar 

  79. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104(3):973–978

    Article  CAS  PubMed  Google Scholar 

  80. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST (2008) Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 13(2):153–166

    Article  CAS  PubMed  Google Scholar 

  81. Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ, Guan XY (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132(7):2542–2556

    Article  CAS  PubMed  Google Scholar 

  82. Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H (2006) Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 351(4):820–824

    Article  CAS  PubMed  Google Scholar 

  83. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121(6):823–835

    Article  CAS  PubMed  Google Scholar 

  84. Koch LK, Zhou H, Ellinger J, Biermann K, Höller T, von Rücker A, Büttner R, Gütgemann I (2008) Stem-cell marker expression in small cell lung carcinoma and developing lung tissue. Hum Pathol 39(11):1597–1605. doi:10.1016/j.humpath.2008.03.008

    Article  CAS  PubMed  Google Scholar 

  85. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65(20):9328–9337

    Article  CAS  PubMed  Google Scholar 

  86. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451(7176):345–349

    Article  CAS  PubMed  Google Scholar 

  87. Schatton T, Frank MH (2008) Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res 21(1):39–55

    Article  CAS  PubMed  Google Scholar 

  88. Immervoll H, Hoem D, Sakariassen PØ, Steffensen OJ, Molven A (2008) Expression of the "stem-cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer 8:48

    Article  PubMed  CAS  Google Scholar 

  89. Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117(Pt 16):3539–3545

    Article  CAS  PubMed  Google Scholar 

  90. Shepherd CJ, Rizzo S, Ledaki I, Davies M, Brewer D, Attard G, de Bono J, Hudson DL (2008) Expression profiling of CD133+ and CD133- epithelial cells from human prostate. Prostate 68(9):1007–1024

    Article  CAS  PubMed  Google Scholar 

  91. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951

    Article  CAS  PubMed  Google Scholar 

  92. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25(12):1696–1708

    Article  CAS  PubMed  Google Scholar 

  93. Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL (2008) CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer 98(4):756–765

    Article  CAS  PubMed  Google Scholar 

  94. Wei C, Guomin W, Yujun L, Ruizhe Q (2007) Cancer stem-like cells in human prostate carcinoma cells DU145: the seeds of the cell line? Cancer Biol Ther 6(5):763–768

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Grosshadern Campus, Medical Center of the University of Munich, Marchioninistr. 15, Munich, 81377, Germany

    Ivan Ischenko, Hendrik Seeliger, Axel Kleespies, Martin K. Angele, Martin E. Eichhorn, Karl-Walter Jauch & Christiane J. Bruns

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  1. Ivan Ischenko
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  2. Hendrik Seeliger
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Correspondence to Ivan Ischenko.

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Ischenko, I., Seeliger, H., Kleespies, A. et al. Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications. Langenbecks Arch Surg 395, 1–10 (2010). https://doi.org/10.1007/s00423-009-0502-z

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  • DOI: https://doi.org/10.1007/s00423-009-0502-z

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