Molecular and Cellular Biochemistry

, Volume 354, Issue 1–2, pp 283–289 | Cite as

Coupled expression of dipeptidyl peptidase-IV and fibroblast activation protein-α in transformed astrocytic cells

  • Eva Balaziova
  • Petr Busek
  • Jarmila Stremenova
  • Lucie Sromova
  • Evzen Krepela
  • Libuse Lizcova
  • Aleksi SedoEmail author


Dipeptidyl peptidase-IV (DPP-IV) and fibroblast activation protein-α (FAP) are speculated to participate in the regulation of multiple biological processes, because of their unique enzymatic activity, as well as by non-hydrolytic molecular interactions. At present, the role of DPP-IV and FAP in the development and progression of various types of tumors, including glioblastoma, is intensively studied, and their functional crosstalk is hypothesized. In this article, we describe the correlative expression of DPP-IV and FAP mRNA in primary cell cultures derived from human glioblastoma and associated expression dynamics of both molecules in astrocytoma cell lines depending on culture conditions. Although the molecular mechanisms of DPP-IV and FAP co-regulations remain unclear, uncoupled expression of transgenic DPP-IV and the endogenous FAP suggests that it occurs rather at the transcriptional than at the posttranscriptional level. Understanding of the expressional and functional coordinations of DPP-IV and FAP may help clarify the mechanisms of biological roles of both molecules in transformed astrocytic cells.


DASH Dipeptidyl peptidase-IV Fibroblast activation protein-α Glioblastoma 



This study was supported by GAUK 99208, GAUK 89607, and MSMT grants 0021620808.


  1. 1.
    Sedo A, Malik R (2001) Dipeptidyl peptidase IV-like molecules: homologous proteins or homologous activities? Biochim Biophys Acta 1550:107–116CrossRefPubMedGoogle Scholar
  2. 2.
    Jacotot E, Callebaut Ch, Blanco J, Krust B, Neubert K, Barth A, Hovanessian G (1996) Dipeptidyl-peptidase IV-β, a novel form of cell-surface-expressed protein with dipeptidyl-peptidase IV activity. Eur J Biochem 239:248–258CrossRefPubMedGoogle Scholar
  3. 3.
    Busek P, Malik R, Sedo A (2004) Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer. Int J Biochem Cell Biol 36:408–421CrossRefPubMedGoogle Scholar
  4. 4.
    Wang XM, Yu DM, Mccaughan GW, Gorrell MD (2005) Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. Hepatology 42:935–945CrossRefPubMedGoogle Scholar
  5. 5.
    Mathew S, Scanlan MJ, Mohan Raj BK, Murty VV, Garin-Chesa P, Old LJ, Rettig WJ, Chaganti RS (1995) The gene for fibroblast activation protein alpha (FAP), a putative cell surface-bound serine protease expressed in cancer stroma and wound healing, maps to chromosome band 2q23. Genomics 25:335–337CrossRefPubMedGoogle Scholar
  6. 6.
    Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH (2008) The role of CD26/dipeptidyl peptidase IV in cancer. Front Biosci 13:1634–1645CrossRefPubMedGoogle Scholar
  7. 7.
    Goscinski MA, Suo ZH, Nesland JM, Chen WT, Zakrzewska M, Wang J, Zhang S, Florenes VA, Giercksky KE (2008) Seprase, dipeptidyl peptidase IV and urokinase-type plasminogen activator expression in dysplasia and invasive squamous cell carcinoma of the esophagus. A study of 229 cases from Anyang Tumor Hospital, Henan Province, China. Oncology 75:49–59CrossRefPubMedGoogle Scholar
  8. 8.
    Ghersi G, Dong H, Goldstein LA, Yeh Y, Hakkinen L, Larjava HS, Chen WT (2002) Regulation of fibroblast migration on collagenous matrix by a cell surface peptidase complex. J Biol Chem 277:29231–29241CrossRefPubMedGoogle Scholar
  9. 9.
    Wesley UV, Albino AP, Tiwari S, Houghton AN (1999) A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med 190:311–322CrossRefPubMedGoogle Scholar
  10. 10.
    Wesley UV, Tiwari S, Houghton AN (2004) Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells. Int J Cancer 109:855–866CrossRefPubMedGoogle Scholar
  11. 11.
    Stremenova J, Krepela E, Mares V, Trim J, Dbaly V, Marek J, Vanickova Z, Lisa V, Yea C, Sedo A (2007) Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade. Int J Oncol 31:785–792PubMedGoogle Scholar
  12. 12.
    Mentlein R, Hattermann K, Hemion C, Jungbluth A, Held-Feindt J (2011) Expression and role of the cell surface protease seprase/fibroblast activation protein-alpha (FAP-alpha) in astroglial tumors. Biol Chem 392:199–207 Google Scholar
  13. 13.
    Scanlan MJ, Raj BK, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, Old LJ, Rettig WJ (1994) Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA 91:5657–5661CrossRefPubMedGoogle Scholar
  14. 14.
    Ghersi G, Zhao Q, Salamone M, Yeh Y, Zucker S, Chen WT (2006) The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. Cancer Res 66:4652–4661CrossRefPubMedGoogle Scholar
  15. 15.
    Sedo A, Malik R, Krepela E (1998) Dipeptidyl peptidase IV in C6 rat glioma cell line differentiation. Biol Chem 379:39–44CrossRefPubMedGoogle Scholar
  16. 16.
    Busek P, Stremenova J, Krepela E, Sedo A (2008) Modulation of substance P signaling by dipeptidyl peptidase-IV enzymatic activity in human glioma cell lines. Physiol Res 57:443–449PubMedGoogle Scholar
  17. 17.
    Sedo A, Malik R, Vicar J, Simanek V, Ulrichova J (2003) Quaternary benzo[c]phenanthridine alkaloids as inhibitors of dipeptidyl peptidase IV-like activity baring enzymes in human blood plasma and glioma cell lines. Physiol Res 52:367–372PubMedGoogle Scholar
  18. 18.
    Lee KN, Jackson KW, Christiansen VJ, Lee CS, Chun JG, Mckee PA (2006) Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein. Blood 107:1397–1404CrossRefPubMedGoogle Scholar
  19. 19.
    Polgar L (2002) The prolyl oligopeptidase family. Cell Mol Life Sci 59:349–362CrossRefPubMedGoogle Scholar
  20. 20.
    Goldstein LA, Chen WT (2000) Identification of an alternatively spliced seprase mRNA that encodes a novel intracellular isoform. J Biol Chem 275:2554–2559CrossRefPubMedGoogle Scholar
  21. 21.
    Niedermeyer J, Scanlan MJ, Garin-Chesa P, Daiber C, Fiebig HH, Old LJ, Rettig WJ, Schnapp A (1997) Mouse fibroblast activation protein: molecular cloning, alternative splicing and expression in the reactive stroma of epithelial cancers. Int J Cancer 71:383–389CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Eva Balaziova
    • 1
  • Petr Busek
    • 1
  • Jarmila Stremenova
    • 1
  • Lucie Sromova
    • 1
  • Evzen Krepela
    • 1
  • Libuse Lizcova
    • 2
  • Aleksi Sedo
    • 1
    Email author
  1. 1.Institute of Biochemistry and Experimental Oncology of the 1st Faculty of MedicineCharles University in PraguePrague 2Czech Republic
  2. 2.Institute of Clinical Biochemistry and Laboratory Diagnostics of the 1st Faculty of MedicineCharles University in Prague and General University Hospital in PraguePrague 2Czech Republic

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