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Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology pp 185–196Cite as

Prominin-1 (CD133) Reveals New Faces of Pancreatic Progenitor Cells and Cancer Stem Cells: Current Knowledge and Therapeutic Perspectives

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 777))

Abstract

Islet transplantation-based therapies were proven successful for type 1 diabetes mellitus, but an extreme shortage of pancreatic islets has motivated recent efforts to develop renewable sources of islet-replacement tissue. Pancreatic progenitor cells hold a promising potential, yet attempts at their prospective isolation are scarce due to the lack of specific marker. We found that prominin-1 (often referred to as CD133 in humans) is expressed by the undifferentiated epithelial cells in the mouse embryonic pancreas. Putative pancreatic epithelial stem and progenitor cells were prospectively enriched in prominin-1+ cell population by cell sorting and characterized. CD133 is also a cell surface marker of human pancreatic cancer stem cells (CSC), which are resistant to conventional treatments such as chemotherapy and radiotherapy. Therefore, a considerable interest in the specific targeting and eradication of CSC is emerging for the cancer therapy, and CD133 may represent a good molecular target. In this chapter, I will summarize our current knowledge about prominin-1/CD133 in mouse and human pancreas.

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References

  1. Bonner-Weir S, Weir GC (2005) New sources of pancreatic beta-cells. Nat Biotechnol 23:857–861

    Article  PubMed  CAS  Google Scholar 

  2. Lumelsky N, Blondel O, Laeng P et al (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394

    Article  PubMed  CAS  Google Scholar 

  3. Hori Y, Rulifson IC, Tsai BC et al (2002) Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci U S A 99:16105–16110

    Article  PubMed  CAS  Google Scholar 

  4. D’Amour KA, Bang AG, Eliazer S et al (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24:1392–1401

    Article  PubMed  Google Scholar 

  5. Tateishi K, He J, Taranova O et al (2008) Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 283:31601–31607

    Article  PubMed  CAS  Google Scholar 

  6. Seaberg RM, Smukler SR, Kieffer TJ et al (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22:1115–1124

    Article  PubMed  CAS  Google Scholar 

  7. Suzuki A, Nakauchi H, Taniguchi H (2004) Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53:2143–2152

    Article  PubMed  CAS  Google Scholar 

  8. Dor Y, Brown J, Martinez OI et al (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46

    Article  PubMed  CAS  Google Scholar 

  9. Gu G, Dubauskaite J, Melton DA (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129:2447–2457

    PubMed  CAS  Google Scholar 

  10. Yin AH, Miraglia S, Zanjani ED et al (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012

    PubMed  CAS  Google Scholar 

  11. Uchida N, Buck DW, He D et al (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97:14720–14725

    Article  PubMed  CAS  Google Scholar 

  12. Kania G, Corbeil D, Fuchs J et al (2005) Somatic stem cell marker prominin-1/CD133 is expressed in embryonic stem cell-derived progenitors. Stem Cells 23:791–804

    Article  PubMed  CAS  Google Scholar 

  13. Corbeil D, Röper K, Hellwig A et al (2000) The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 275:5512–5520

    Article  PubMed  CAS  Google Scholar 

  14. Hori Y, Fukumoto M, Kuroda Y (2008) Enrichment of putative pancreatic progenitor cells from mice by sorting for prominin1 (CD133) and platelet-derived growth factor receptor ß. Stem Cells 26:2912–2920

    Article  PubMed  CAS  Google Scholar 

  15. Oshima Y, Suzuki A, Kawashimo K et al (2007) Isolation of mouse pancreatic ductal progenitor cells expressing CD133 and c-Met by flow cytometric cell sorting. Gastroenterology 132:720–732

    Article  PubMed  CAS  Google Scholar 

  16. Sugiyama T, Rodriguez RT, McLean GW et al (2007) Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS. Proc Natl Acad Sci U S A 104:175–180

    Article  PubMed  CAS  Google Scholar 

  17. Koblas T, Pektorova L, Zacharovova K et al (2008) Differentiation of CD133-positive pancreatic cells into insulin-producing islet-like cell clusters. Transplant Proc 40:415–418

    Article  PubMed  CAS  Google Scholar 

  18. Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17:387–403

    Article  PubMed  CAS  Google Scholar 

  19. Stingl J, Eirew P, Ricketson I et al (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439:993–997

    PubMed  CAS  Google Scholar 

  20. Shackleton M, Vaillant F, Simpson KJ et al (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88

    Article  PubMed  CAS  Google Scholar 

  21. Minami K, Okuno M, Miyawaki K et al (2005) Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci USA 102:15116–15121

    Article  PubMed  CAS  Google Scholar 

  22. Zhou Q, Brown J, Kanarek A et al (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:627–632

    Article  PubMed  CAS  Google Scholar 

  23. Houbracken I, de Waele E, Larden J et al (2011) Lineage tracing evidence for transdifferentiation of acinar to duct cells and plasticity of human pancreas. Gastroenterology 141:731–741

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Baccelli I, Trumpp A (2012) The evolving concept of cancer and metastasis stem cells. J Cell Biol 198:281–293

    Article  PubMed  CAS  Google Scholar 

  26. Li C, Heidt DG, Dalerba P et al (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    Article  PubMed  CAS  Google Scholar 

  27. Immervoll H, Hoem D, Steffensen OJ et al (2011) Visualization of CD44 and CD133 in normal pancreas and pancreatic ductal adenocarcinomas: non-overlapping membrane expression in cell populations positive for both markers. J Histochem Cytochem 59:441–455

    Article  PubMed  CAS  Google Scholar 

  28. Shimizu K, Itoh T, Shimizu M et al (2009) CD133 expression pattern distinguishes intraductal papillary mucinous neoplasms from ductal adenocarcinomas of the pancreas. Pancreas Nov 38(8):e207–e214

    Article  Google Scholar 

  29. Karbanová J, Missol-Kolka E, Fonseca AV et al (2008) The stem cell marker CD133 (Prominin-1) is expressed in various human glandular epithelia. J Histochem Cytochem 56:977–993

    Article  PubMed  Google Scholar 

  30. Lardon J, Corbeil D, Huttner WB et al (2008) Stem cell marker prominin-1/AC133 is expressed in duct cells of the adult human pancreas. Pancreas 36:e1–e6

    Article  PubMed  Google Scholar 

  31. Immervoll H, Hoem D, Sakariassen P et al (2008) Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer 8:48

    Article  PubMed  Google Scholar 

  32. Miyamoto Y, Maitra A, Ghosh B et al (2003) Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell 3:565–576

    Article  PubMed  CAS  Google Scholar 

  33. Stanger BZ, Stiles B, Lauwers GY et al (2005) Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 8:185–195

    Article  PubMed  CAS  Google Scholar 

  34. Hermann PC, Huber SL, Herrler T et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323

    Article  PubMed  CAS  Google Scholar 

  35. Kayali AG, Lopez AD, Hao E et al (2012) The SDF-1α/CXCR4 Axis is required for proliferation and maturation of human fetal pancreatic endocrine progenitor cells. PLoS One 7:e38721

    Article  PubMed  CAS  Google Scholar 

  36. Moriyama T, Ohuchida K, Mizumoto K et al (2010) Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells. Cancer 116:3357–3368

    Article  PubMed  CAS  Google Scholar 

  37. Hashimoto O, Shimizu K, Semba S et al (2011) Hypoxia induces tumor aggressiveness and the expansion of CD133-positive cells in a hypoxia-inducible factor-1α-dependent manner in pancreatic cancer cells. Pathobiology 78:181–192

    Article  PubMed  CAS  Google Scholar 

  38. Freund D, Bauer N, Boxberger S et al (2006) Polarization of human hematopoietic progenitors during contact with multipotent mesenchymal stromal cells: effects on proliferation and clonogenicity. Stem Cells Dev 15:815–829

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

I would like to thank Drs. Kazuya Shimizu and Okito Hashimoto for valuable comments on the manuscript. I am also grateful to Norito Fujiwara, Rina Hirai, Yuki Kamino, Nancy Katayama, and Takuma Miura for their technical help. This research was supported by Grants-in-Aid (21591773, 23592007, 24592025) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Science, 7-10-2 Tomogaoka, Suma-ku, Kobe, 654-0142, Japan

    Yuichi Hori M.D., Ph.D.

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  1. Yuichi Hori M.D., Ph.D.
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Correspondence to Yuichi Hori M.D., Ph.D. .

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Editors and Affiliations

  1. , Biotechnological Centre (BIOTEC), Dresden University of Technology, Fetscherstr. 74, Dresden, 01307, Sachsen, Germany

    Denis Corbeil

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Hori, Y. (2013). Prominin-1 (CD133) Reveals New Faces of Pancreatic Progenitor Cells and Cancer Stem Cells: Current Knowledge and Therapeutic Perspectives. In: Corbeil, D. (eds) Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology. Advances in Experimental Medicine and Biology, vol 777. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5894-4_12

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