Assessment of CD133-positive extracellular membrane vesicles in pancreatic cancer ascites and beyond

  • Christine A. Fargeas
  • Jana Karbanová
  • Denis CorbeilEmail author
Letter to the editor

To the Editor,

In a recent publication released online (February, 25 2019; in Medical Molecular Morphology and entitled “Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer”, Sakaue and colleagues propose that highly glycosylated CD133 may serve as a potential prognostic biomarker for pancreatic cancer. Their conclusions are partly based on the discrimination of CD133 immunoreactivities on Western blot [1]. Unfortunately, essential information emerging from earlier studies that might have driven the rationale or design of the present investigation was not provided. This includes the expression of CD133 (Prominin-1) in healthy and cancerous tissues notably pancreas and, importantly, its association with extracellular membrane vesicles (EVs). Similarly, several features regarding CD133 biology, including its role in membrane dynamics and remodeling of cellular...


Biomarker Cancer CD133 Ectosome Exosome Prominin-1 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Sakaue T, Koga H, Iwamoto H, Nakamura T, Ikezono Y, Abe M, Wada F, Masuda A, Tanaka T, Fukahori M, Ushijima T, Mihara Y, Naitou Y, Okabe Y, Kakuma T. Ohta K, Nakamura KI, Torimura T (2019) Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer. Med Mol Morphol. (epub ahead of print) Google Scholar
  2. 2.
    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):313–323CrossRefGoogle Scholar
  3. 3.
    Heiler S, Wang Z, Zöller M (2016) Pancreatic cancer stem cell markers and exosomes—the incentive push. World J Gastroenterol 22(26):5971–6007CrossRefGoogle Scholar
  4. 4.
    Lee YJ, Wu CC, Li JW, Ou CC, Hsu SC, Tseng HH, Kao MC, Liu JY (2016) A rational approach for cancer stem-like cell isolation and characterization using CD44 and prominin-1(CD133) as selection markers. Oncotarget 7(48):78499–78515Google Scholar
  5. 5.
    Lardon J, Corbeil D, Huttner WB, Ling Z, Bouwens L (2008) Stem cell marker prominin-1/AC133 is expressed in duct cells of the adult human pancreas. Pancreas 36(1):e1–e6CrossRefGoogle Scholar
  6. 6.
    Immervoll H, Hoem D, Sakariassen P, Steffensen OJ, Molven A (2008) Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer 8:48CrossRefGoogle Scholar
  7. 7.
    Karbanová J, Missol-Kolka E, Fonseca AV, Lorra C, Janich P, Hollerová H, Jászai J, Ehrmann J, Kolár Z, Liebers C, Arl S, Subrtová D, Freund D, Mokrý J, Huttner WB. Corbeil D (2008) The stem cell marker CD133 (prominin-1) is expressed in various human glandular epithelia. J Histochem Cytochem 56(11):977–993CrossRefGoogle Scholar
  8. 8.
    Florek M, Haase M, Marzesco AM, Freund D, Ehninger G, Huttner WB, Corbeil D (2005) Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. Cell Tissue Res 319(1):15–26CrossRefGoogle Scholar
  9. 9.
    Marzesco AM, Janich P, Wilsch-Bräuninger M, Dubreuil V, Langenfeld K, Corbeil D, Huttner WB (2005) Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci 118(Pt 13):2849–2858CrossRefGoogle Scholar
  10. 10.
    Huttner HB, Janich P, Köhrmann M, Jászai J, Siebzehnrubl F, Blümcke I, Suttorp M, Gahr M, Kuhnt D, Nimsky C, Krex D, Schackert G, Löwenbrück K, Reichmann H, Jüttler E. Hacke W, Schellinger PD, Schwab S, Wilsch-Bräuninger M, Marzesco AM, Corbeil D (2008) The stem cell marker prominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease. Stem Cells 26(3):698–705CrossRefGoogle Scholar
  11. 11.
    Marzesco AM (2013) Prominin-1-containing membrane vesicles: origins, formation, and utility. Adv Exp Med Biol 777:41–54CrossRefGoogle Scholar
  12. 12.
    Bauer N, Wilsch-Bräuninger M, Karbanová J, Fonseca AV, Strauss D, Freund D, Thiele C, Huttner WB, Bornhäuser M, Corbeil D (2011) Haematopoietic stem cell differentiation promotes the release of prominin-1/CD133-containing membrane vesicles—a role of the endocytic-exocytic pathway. EMBO Mol Med 3(7):398–409CrossRefGoogle Scholar
  13. 13.
    Rappa G, Mercapide J, Anzanello F, Le TT, Johlfs MG, Fiscus RR, Wilsch-Bräuninger M, Corbeil D, Lorico A (2013) Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells. Exp Cell Res 319(6):810–819CrossRefGoogle Scholar
  14. 14.
    Chao OS, Chang TC, Di Bella MA, Alessandro R, Anzanello F, Rappa G, Goodman OB, Lorico A (2017) The HDAC6 inhibitor tubacin induces release of CD133(+) extracellular vesicles from cancer cells. J Cell Biochem 118(12):4414–4424CrossRefGoogle Scholar
  15. 15.
    Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Théry C (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA 113(8):E968–E977CrossRefGoogle Scholar
  16. 16.
    Bobinger T, May L, Lücking H, Kloska SP, Burkardt P, Spitzer P, Maler JM, Corbeil D, Huttner HB (2017) CD133-positive membrane particles in cerebrospinal fluid of patients with inflammatory and degenerative neurological diseases. Front Cell Neurosci 11:77CrossRefGoogle Scholar
  17. 17.
    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(12):5013–5021Google Scholar
  18. 18.
    Zhou F, Cui C, Ge Y, Chen H, Li Q, Yang Z, Wu G, Sun S, Chen K, Gu J, Jiang J, Wei Y (2010) Alpha2,3-Sialylation regulates the stability of stem cell marker CD133. J Biochem 148(3):273–280CrossRefGoogle Scholar
  19. 19.
    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(8):5512–5520CrossRefGoogle Scholar
  20. 20.
    Karbanová J, Laco J, Marzesco AM, Janich P, Voborníková M, Mokrý J, Fargeas CA, Huttner WB, Corbeil D (2014) Human prominin-1 (CD133) is detected in both neoplastic and non-neoplastic salivary gland diseases and released into saliva in a ubiquitinated form. PLoS One 9(6):e98927CrossRefGoogle Scholar
  21. 21.
    Boivin D, Labbé D, Fontaine N, Lamy S, Beaulieu E, Gingras D, Béliveau R (2009) The stem cell marker CD133 (prominin-1) is phosphorylated on cytoplasmic tyrosine-828 and tyrosine-852 by Src and Fyn tyrosine kinases. Biochemistry 48(18):3998–4007CrossRefGoogle Scholar
  22. 22.
    Yang F, Xing Y, Li Y, Chen X, Jiang J, Ai Z, Wei Y (2018) Monoubiquitination of cancer stem cell marker CD133 at lysine 848 regulates Its secretion and promotes cell migration. Mol Cell Biol 38(15):e00024–e00018CrossRefGoogle Scholar
  23. 23.
    Corbeil D, Karbanová J, Fargeas CA, Jászai J (2013) Prominin-1 (CD133): molecular and cellular features across species. Adv Exp Med Biol 777:3–24CrossRefGoogle Scholar
  24. 24.
    Bidlingmaier S, Zhu X, Liu B (2008) The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J Mol Med (Berl) 86(9):1025–1032CrossRefGoogle Scholar
  25. 25.
    Thamm K, Graupner S, Werner C, Huttner WB, Corbeil D (2016) Monoclonal antibodies 13A4 and AC133 do not recognize the canine ortholog of mouse and human stem cell antigen prominin-1 (CD133). PLoS One 11(10):e0164079CrossRefGoogle Scholar
  26. 26.
    Pötgens AJ, Schmitz U, Kaufmann P, Frank HG (2002) Monoclonal antibody CD133-2 (AC141) against hematopoietic stem cell antigen CD133 shows crossreactivity with cytokeratin 18. J Histochem Cytochem 50(8):1131–1134CrossRefGoogle Scholar

Copyright information

© The Japanese Society for Clinical Molecular Morphology 2019

Authors and Affiliations

  1. 1.Tissue Engineering Laboratories, Biotechnology Center (BIOTEC) and Center for Molecular and Cellular Bioengineering (CMCB)Technische Universität DresdenDresdenGermany

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