Display options
Cite
Lenggenhager D, Curioni-Fontecedro A, Storz M, et al. An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative. Transl Oncol. 2014;7(2):206-12doi: 10.1016/j.tranon.2014.02.018.
Lenggenhager, D., Curioni-Fontecedro, A., Storz, M., Shakhova, O., Sommer, L., Widmer, D. S., Seifert, B., Moch, H., Dummer, R., & Mihic-Probst, D. (2014). An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative. Translational oncology, 7(2), 206-12. https://doi.org/10.1016/j.tranon.2014.02.018
Lenggenhager, Daniela, et al. "An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative." Translational oncology vol. 7,2 (2014): 206-12. doi: https://doi.org/10.1016/j.tranon.2014.02.018
Lenggenhager D, Curioni-Fontecedro A, Storz M, Shakhova O, Sommer L, Widmer DS, Seifert B, Moch H, Dummer R, Mihic-Probst D. An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative. Transl Oncol. 2014 Apr;7(2):206-12. doi: 10.1016/j.tranon.2014.02.018. Epub 2014 Apr 17. PMID: 24746711; PMCID: PMC4101291.
Copy Download .nbib Format: NLM
Share it on

Transl Oncol. 2014 Apr;7(2):206-12. doi: 10.1016/j.tranon.2014.02.018. Epub 2014 Apr 17.

An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative.

Translational oncology

Daniela Lenggenhager, Alessandra Curioni-Fontecedro, Martina Storz, Olga Shakhova, Lukas Sommer, Daniel S Widmer, Burkhardt Seifert, Holger Moch, Reinhard Dummer, Daniela Mihic-Probst

Affiliations

  1. Institute of Surgical Pathology, University Hospital, Zurich, Switzerland.
  2. Department of Oncology, University Hospital, Zurich, Switzerland.
  3. Institute of Anatomy, University of Zurich, Zurich, Switzerland.
  4. Clinic of Dermatology, University Hospital, Zurich, Switzerland.
  5. Division of Biostatistics, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
  6. Institute of Surgical Pathology, University Hospital, Zurich, Switzerland. Electronic address: [email protected].

PMID: 24746711 PMCID: PMC4101291 DOI: 10.1016/j.tranon.2014.02.018

Abstract

Despite existing vaccination strategies targeting TRP-2, its function is not yet fully understood. TRP-2 is an enzyme involved in melanin biosynthesis and therefore discussed as a differentiation antigen. However, in mice Trp-2 was shown to be expressed in melanocyte stem cells of the hair follicle and therefore also considered as an indicator of stemness. A proper understanding of the TRP-2 function is crucial, considering a vaccination targeting cells with stemness properties would be highly effective in contrast to a therapy targeting differentiated melanoma cells. Analysing over 200 melanomas including primaries, partly matched metastases and patients' cell cultures we show that TRP-2 is correlated with Melan A expression and decreases with tumor progression. In mice it is expressed in differentiated melanocytes as well as in stem cells. Furthermore, we identify a TRP-2 negative, proliferative, hypoxia related cell subpopulation which is significantly associated with tumor thickness and diseases progression. Patients with a higher percentage of those cells have a less favourable tumor specific survival. Our findings underline that TRP-2 is a differentiation antigen, highlighting the importance to combine TRP-2 vaccination with other strategies targeting the aggressive undifferentiated hypoxia related subpopulation.

Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

References

  1. Nat Rev Cancer. 2003 Oct;3(10):721-32 - PubMed
  2. Nat Med. 2012 May 04;18(5):636-7 - PubMed
  3. Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4783-8 - PubMed
  4. J Invest Dermatol. 2013 Oct;133(10):2436-2443 - PubMed
  5. Cancer. 1995 Jan 15;75(2 Suppl):735-41 - PubMed
  6. Nature. 2002 Apr 25;416(6883):854-60 - PubMed
  7. Cancer Res. 2009 Dec 1;69(23):9012-9 - PubMed
  8. Brain Res Mol Brain Res. 1998 Jan;53(1-2):307-10 - PubMed
  9. Nat Cell Biol. 2012 Aug;14(8):882-90 - PubMed
  10. J Biol Chem. 2006 Oct 13;281(41):30678-83 - PubMed
  11. Int J Cancer. 2007 Oct 15;121(8):1764-70 - PubMed
  12. PLoS One. 2010 Sep 10;5(9): - PubMed
  13. J Exp Med. 1994 Mar 1;179(3):921-30 - PubMed
  14. Am J Pathol. 1996 May;148(5):1567-76 - PubMed
  15. Semin Surg Oncol. 1992 Nov-Dec;8(6):400-14 - PubMed
  16. Cancer Res. 1998 Nov 1;58(21):4895-901 - PubMed
  17. Trends Genet. 1993 Apr;9(4):138-41 - PubMed
  18. Biochim Biophys Acta. 2009 Dec;1796(2):293-308 - PubMed
  19. Science. 1991 Dec 13;254(5038):1643-7 - PubMed
  20. Vaccine. 2010 Nov 23;28(50):7837-43 - PubMed
  21. Gene Ther. 2000 Feb;7(3):249-54 - PubMed
  22. Oncogene. 2012 May 10;31(19):2461-70 - PubMed
  23. J Natl Cancer Inst. 1996 Nov 20;88(22):1635-44 - PubMed
  24. Int J Cancer. 2006 May 1;118(9):2262-8 - PubMed
  25. Immunity. 1995 Feb;2(2):167-75 - PubMed
  26. J Exp Med. 1995 Sep 1;182(3):689-98 - PubMed
  27. J Exp Med. 1996 Dec 1;184(6):2207-16 - PubMed
  28. J Exp Med. 1997 Feb 3;185(3):453-9 - PubMed
  29. Nature. 2010 Jun 3;465(7298):577-83 - PubMed

Publication Types