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Konstitutive Expression des potentiellen Stammzellmarkers CD44 in permanenten HNSCC-Zelllinien

Constitutive expression of the potential stem cell marker CD44 in permanent HNSCC cell lines

Zusammenfassung

Hintergrund

Trotz der steten Entwicklung neuer Diagnose- und Behandlungsmethoden konnte die Überlebensrate von Patienten mit Plattenepithelkarzinomen im Kopf-Hals-Bereich („head and neck squamous cell carcinoma“, HNSCC) in den vergangenen Jahrzehnten nicht entscheidend verbessert werden. Dies unterstreicht die dringende Notwendigkeit der Entwicklung innovativer immuntherapeutischer Ansätze. In diesem Zusammenhang wird zunehmend deutlich, dass Stammzellen an der Entstehung und Progression von Tumoren maßgeblich beteiligt sind. Deren Identität sowie die zugrunde liegenden zellulären und molekularen Mechanismen sind jedoch bei Kopf-Hals-Karzinomen weitestgehend unbekannt.

Material und Methoden

Tumoren des Kopf-Hals-Bereichs sowie die Zellen des peripheren Bluts von Patienten mit HNSCC wurden mittels Durchflusszytometrie hinsichtlich der Expression verschiedener potentieller Stammzellmarker untersucht.

Ergebnisse

Es konnten distinkte CD44-positive, lin-negative Zellpopulationen innerhalb der HNSCC-Einzelzellsuspensionen identifiziert werden, jedoch mit starken individuellen Abweichungen. Überraschenderweise zeigen unsere Untersuchungen, dass der potentielle Stammzellmarker CD44 konstitutiv von allen untersuchten permanenten HNSCC-Zelllinien auf der Zelloberfläche exprimiert wird.

Schlussfolgerungen

Unsere Daten lassen stark vermuten, dass CD44-positive Tumorstammzellen möglicherweise auch eine Schlüsselrolle bei der Etablierung permanenter HNSCC-Zelllinien spielen. Dabei findet eine Selektion besonders robuster Zellpopulationen statt, die im wirklichen Leben möglicherweise die Progression und Metastasierung von HNSCC vorantreiben. Weitere Stammzellmarker werden hinsichtlich ihrer Expression und Funktion untersucht werden.

Abstract

Background

Despite significant advances and the use of new diagnosic and therapy methods to treat head and neck squamous cell carcinoma (HNSCC), prognosis has improved only marginally in the last decades. Thus, there is an enormous need for novel immunotherapeutic approaches. It is becoming more and more obvious that stem cells play an important role in tumor development and progression. The identity of these cells and the underlying cellular and molecular mechanisms remain mostly unknown in HNSCC.

Material and methods

Solid tumors as well as cells from the peripheral blood of patients with HNSCC were analyzed by flow cytometry concerning the expression of different putative stem cell marker proteins.

Results

Distinct populations of CD44-positive (CD44+), lin-negative (lin-) potential stem cells could be identified in solid tumors of HNSCC patients with strong individual variations. Surprisingly, the potential stem cell marker CD44 was found to be constitutively expressed on the surface of all permanent HNSCC cell lines analyzed.

Conclusion

These data strongly suggest that CD44+ tumor stem cells may play a key role in establishment of permanent HNSCC cell lines, selecting especially robust cell entities that in real life might drive progression and metastasis of HNSCC. Individual analysis of tumor stem cell markers will be an important tool for innovative therapies and prognosis of patients with HNSCC. Additional stem cell markers will be investigated concerning their expression and cellular function.

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Literatur

  1. Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V. in Zusammenarbeit mit dem Robert-Koch-Institut (Hrsg) (2006) Krebs in Deutschland, Häufigkeiten und Trends, 5. Aufl. Gekid, Saarbrücken

  2. Vokes EE, Weichselbaum RR, Lippman SM, Hong WK (1993) Head and neck cancer. N Engl J Med 328: 184–194

    PubMed  Article  CAS  Google Scholar 

  3. Mantovani G, Bianchi A, Curreli L, Ghiani M et al. (1994) Neo-adjuvant chemotherapy +/- immunotherapy with s.c. IL2 in advanced squamous cell carcinoma of the head and neck: a pilot study. Biotherapy 8: 91–98

    PubMed  Article  CAS  Google Scholar 

  4. Liu S, Yang H, Liang C (2002) Combined IL-2 and IL-12 gene therapy for murine head and neck squamous cell carcinoma. Zhonghua Zhong Liu Za Zhi 24: 323–326

    PubMed  CAS  Google Scholar 

  5. Vokes EE, Weichselbaum RR (1993) Measurable impact: multimodality therapy of head and neck cancer. Int J Radiat Oncol Biol Phys 27: 481–482

    PubMed  CAS  Google Scholar 

  6. Chin D, Boyle GM, Porceddu S et al. (2006) Head and neck cancer: past, present and future. Expert Rev Anticancer Ther 6: 1111–1118

    PubMed  Article  Google Scholar 

  7. Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S (2000) Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 74: 181–273

    PubMed  CAS  Article  Google Scholar 

  8. Pries R, Wollenberg B (2006) Cytokines in head and neck cancer. Cytokine Growth Factor Rev 17: 141–146

    PubMed  Article  CAS  Google Scholar 

  9. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414: 105–111

    PubMed  Article  CAS  Google Scholar 

  10. Wang J, Xi L, Gooding W et al. (2005) Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck. Adv Otorhinolaryngol 62: 121–133

    PubMed  CAS  Google Scholar 

  11. Jordan CT (2004) Cancer stem cell biology: from leukemia to solid tumors. Curr Opin Cell Biol 16: 708–712

    PubMed  Article  CAS  Google Scholar 

  12. Jordan CT, Guzman ML, Noble M (2006) Cancer stem cells. N Engl J Med 355: 1253–1261

    PubMed  Article  CAS  Google Scholar 

  13. Prince ME, Sivanandan R, Kaczorowski A et al. (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: 973–978

    PubMed  Article  CAS  Google Scholar 

  14. Kawamata H, Nakashiro K, Uchida D et al. (1997) Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral-squamous-cancer cell lines. Int J Cancer 70: 120–127

    PubMed  Article  CAS  Google Scholar 

  15. Rangan SR (1972) A new human cell line (FaDu) from a hypopharyngeal carcinoma. Cancer 29: 117–121

    PubMed  Article  CAS  Google Scholar 

  16. Takebayashi S, Hickson A, Ogawa T et al. (2004) Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer. Genes Chromosomes Cancer 41: 145–154

    PubMed  Article  CAS  Google Scholar 

  17. Ellison BS, Zanin M KB, Boackle RJ (2007) Complement susceptibility in glutamine deprived breast cancer cells. Cell Div 2: 20

    PubMed  Article  CAS  Google Scholar 

  18. Baldwin WS, Curtis SW, Cauthen CA et al. (1998) BG-1 ovarian cell line: an alternative model for examining estrogen-dependent growth in vitro. In Vitro Cell Dev Biol Anim 34: 649–654

    PubMed  Article  CAS  Google Scholar 

  19. Sozzani S, Luini W, Borsatti A et al. (1997) Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. J Immunol 159: 1993–2000

    PubMed  CAS  Google Scholar 

  20. Subramaniam V, Vincent IR, Gardner H, Chan E. et al. (2007) CD44 regulates cell migration in human colon cancer cells via Lyn kinase and AKT phosphorylation. Exp Mol Pathol 83: 207–215

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  22. Dontu G, Al-Hajj M, Abdallah WM et al. (2003) Stem cells in normal breast development and breast cancer. Cell Prolif (Suppl 1) 36: 59–72

    Google Scholar 

  23. Southam CM (1960) Relationships of immunology to cancer: a review. Cancer Res 20: 271–291

    PubMed  CAS  Google Scholar 

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Correspondence to B. Wollenberg.

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Pries, R., Wittkopf, N., Hasselbacher, K. et al. Konstitutive Expression des potentiellen Stammzellmarkers CD44 in permanenten HNSCC-Zelllinien. HNO 56, 461–466 (2008). https://doi.org/10.1007/s00106-008-1707-0

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  • DOI: https://doi.org/10.1007/s00106-008-1707-0

Schlüsselwörter

  • Kopf-Hals-Karzinom
  • Tumorstammzelle
  • Immuntherapie

Keywords

  • Head and neck cancer
  • Tumor stem cells
  • Immunotherapy