Cell and Tissue Research

, Volume 319, Issue 1, pp 15–26 | Cite as

Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer

  • Mareike Florek
  • Michael Haase
  • Anne-Marie Marzesco
  • Daniel Freund
  • Gerhard Ehninger
  • Wieland B. Huttner
  • Denis CorbeilEmail author
Regular Article


Human prominin-1/CD133 has been reported to be expressed in neural and hematopoietic stem/progenitor cells and in embryonic, but not adult, epithelia. This lack of detection of human prominin-1, as defined by its glycosylation-dependent AC133 epitope, is surprising given the expression of the murine ortholog in adult epithelia. Here, we demonstrate, by using a novel prominin-1 antiserum (αhE2), that the decrease of AC133 immunoreactivity observed during differentiation of the colonic adenocarcinoma-derived Caco-2 cells is not paralleled by a down-regulation of prominin-1. We have also shown that αhE2 immunoreactivity, but not AC133 immunoreactivity, is present in several adult human tissues, such as kidney proximal tubules and the parietal layer of Bowman’s capsule of juxtamedullary nephrons, and in lactiferous ducts of the mammary gland. These observations suggest that only the AC133 epitope is down-regulated upon cell differentiation. Furthermore, αhE2 immunoreactivity has been detected in several kidney carcinomas derived from proximal tubules, independent of their grading. Interestingly, in one particular case, the AC133 epitope, which is restricted to stem cells in normal adult tissue, was up-regulated in the vicinity of the tumor. Our data thus show that (1) in adults, the expression of human prominin-1 is not limited to stem and progenitor cells, and (2) the epitopes of prominin-1 might be useful for investigating solid cancers.


Prominin-1 (CD133) Epithelial cells Differentiation Cancer Human 



We thank D. Buck for the human prominin-1 cDNA, G. Baretton for human tissue samples, I. Peterson for her excellent sample preparation, I. Nüβlein for her valuable assistance with FACS, and S. Langer for valuable technical assistance with some immunohistochemistry experiments.


  1. Baersch G, Baumann M, Ritter J, Jurgens H, Vormoor J (1999) Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia. Br J Haematol 107:572–580CrossRefPubMedGoogle Scholar
  2. Bhatia M (2001) AC133 expression in human stem cells. Leukemia 15:1685–1688PubMedGoogle Scholar
  3. Bornhäuser M, Eger L, Oelschlaegel U, Auffermann-Gretzinger S, Kiani A, Schetelig J, Illmer T, Schaich M, Corbeil D, Thiede C, Ehninger G (2004) Rapid reconstitution of dendritic cells after allogeneic transplatation of CD133+ selected hematopoietic stem cells. Leukemia (in press).  DOI 10.1038/sj.leu.2403563
  4. Buhring HJ, Seiffert M, Bock TA, Scheding S, Thiel A, Scheffold A, Kanz L, Brugger W (1999) Expression of novel surface antigens on early hematopoietic cells. Ann N Y Acad Sci 872:25–38PubMedGoogle Scholar
  5. Corbeil D, Röper K, Weigmann A, Huttner WB (1998) AC133 hematopoietic stem cell antigen—human homologue of mouse kidney prominin or distinct member of a novel protein family. Blood 91:2625–2626PubMedGoogle Scholar
  6. Corbeil D, Röper K, Hannah MJ, Hellwig A, Huttner WB (1999) Selective localization of the polytopic membrane protein prominin in microvilli of epithelial cells—a combination of apical sorting and retention in plasma membrane protrusions. J Cell Sci 112:1023–1033PubMedGoogle Scholar
  7. Corbeil D, Röper K, Hellwig A, Tavian M, Miraglia S, Watt SM, Simmons PJ, Peault B, Buck DW, Huttner WB (2000) The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 275:5512–5520CrossRefPubMedGoogle Scholar
  8. Corbeil D, Fargeas CA, Huttner WB (2001a) Rat prominin, like its mouse and human orthologues, is a pentaspan membrane glycoprotein. Biochem Biophys Res Commun 285:939–944CrossRefPubMedGoogle Scholar
  9. Corbeil D, Röper K, Fargeas CA, Joester A, Huttner WB (2001b) Prominin: a story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2:82–91CrossRefPubMedGoogle Scholar
  10. Fargeas CA, Corbeil D, Huttner WB (2003a) AC133 antigen, CD133, prominin-1, prominin-2, etc.: prominin family gene products in need of a rational nomenclature. Stem Cells 21:506–508CrossRefPubMedGoogle Scholar
  11. Fargeas CA, Florek M, Huttner WB, Corbeil D (2003b) Characterization of prominin-2, a new member of the prominin family of pentaspan membrane glycoproteins. J Biol Chem 278:8586–8596CrossRefPubMedGoogle Scholar
  12. Fargeas CA, Joester A, Missol-Kolka E, Hellwig A, Huttner WB, Corbeil D (2004) Identification of novel prominin-1/CD133 splice variants with alternative C-termini and their expression in epididymis and testis. J Cell Sci 117:4301–4311CrossRefPubMedGoogle Scholar
  13. Giebel B, Corbeil D, Beckmann J, Höhn J, Freund D, Giesen K, Fischer J, Kögler G, Wernet P (2004) Segregation of lipid raft markers including CD133 in polarized human hematopoietic stem and progenitor cells. Blood 104:2332–2338CrossRefPubMedGoogle Scholar
  14. Green CL, Loken M, Buck D, Deeg HJ (2000) Discordant expression of AC133 and AC141 in patients with myelodysplastic syndrome (MDS) and acute myelogeneous leukemia (AML). Leukemia 14:770–772CrossRefPubMedGoogle Scholar
  15. Handgretinger R, Gordon PR, Leimig T, Chen X, Buhring HJ, Niethammer D, Kuci S (2003) Biology and plasticity of CD133+ hematopoietic stem cells. Ann N Y Acad Sci 996:141–151PubMedGoogle Scholar
  16. Kratz-Albers K, Zuhlsdorp M, Leo R, Berdel WL, Buchner T, Serve H (1998) Expression of a AC133, a novel stem cell marker, on human leukemic blasts lacking CD34-antigen and on a human CD34+ leukemic line:MUTZ-2. Blood 92:4485–4487PubMedGoogle Scholar
  17. Maw MA, Corbeil D, Koch J, Hellwig A, Wilson-Wheeler JC, Bridges RJ, Kumaramanickavel G, John S, Nancarrow D, Röper K, Weigmann A, Huttner WB, Denton MJ (2000) A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum Mol Genet 9:27–34CrossRefPubMedGoogle Scholar
  18. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90:5013–5021PubMedGoogle Scholar
  19. Miraglia S, Godfrey W, Buck D (1998) A response to AC133 hematopoietic stem cell antigen: human homologue of mouse kidney prominin or distinct member of a novel protein family? Blood 91:4390–4391PubMedGoogle Scholar
  20. Ogier-Denis E, Codogno P, Chantret I, Trugnan G (1988) The processing of asparagine-linked oligosaccharides in HT-29 cells is a function of their state of enterocytic differentiation. An accumulation of Man9,8-GlcNAc2-Asn species is indicative of an impaired N-glycan trimming in undifferentiated cells. J Biol Chem 263:6031–6037PubMedGoogle Scholar
  21. Pinto M, Robine-Leon S, Appay MD, Kedinger M, Triadou N, Dussaulx E, Lacroix B, Simon-Assamnn P, Haffen K, Fogh J, Zweibaum A (1983) Enterocyte-like differentiation and polarization of the human-colon carcinoma cell-line CACO-2 in culture. Biol Cell 47:323–330Google Scholar
  22. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 415:105–111CrossRefGoogle Scholar
  23. Röper K, Corbeil D, Huttner WB (2000) Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane. Nat Cell Biol 2:582–592CrossRefPubMedGoogle Scholar
  24. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97:14720–14725CrossRefPubMedGoogle Scholar
  25. Waller CF, Martens UM, Lange W (1999) Philadelphia chromosome-positive cells are equally distributed in AC133+ and AC133− fractions of CD34+ peripheral blood progenitor cells from patients with CML. Leukemia 13:1466–1467CrossRefPubMedGoogle Scholar
  26. Weigmann A, Corbeil D, Hellwig A, Huttner WB (1997) Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci USA 94:12425–12430CrossRefPubMedGoogle Scholar
  27. Wuchter C, Ratei R, Spahn G, Schoch C, Harbott J, Schnittger S, Haferlach T, Creutzig U, Sperling C, Karawajew L, Ludwig WD (2001) Impact of CD133 (AC133) and CD90 expression analysis for acute leukemia immunophenotyping. Haematologica 86:154–161PubMedGoogle Scholar
  28. Wynter EA de, Buck D, Hart C, Heywood R, Coutinho LH, Clayton A, Rafferty JA, Burt D, Guenechea G, Bueren JA, Gagen D, Fairbairn LJ, Lord BI, Testa NG (1998) CD34+ AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells 16:387–396PubMedGoogle Scholar
  29. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Mareike Florek
    • 1
  • Michael Haase
    • 2
  • Anne-Marie Marzesco
    • 3
  • Daniel Freund
    • 1
  • Gerhard Ehninger
    • 1
  • Wieland B. Huttner
    • 3
  • Denis Corbeil
    • 1
    • 3
    Email author
  1. 1.Medical Clinic and Polyclinic IUniversity Carl Gustav CarusDresdenGermany
  2. 2.Department of PathologyUniversity Carl Gustav CarusDresdenGermany
  3. 3.Max-Planck-Institute of Molecular Cell Biology and GeneticsDresdenGermany

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