Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil

  • Authors:
    • Tobias Engl
    • Borna Relja
    • Iyad Natsheh
    • Jasmina Makarevic
    • Iris Müller
    • Wolf-Dietrich Beecken
    • Dietger Jonas
    • Roman A. Blaheta
  • View Affiliations

  • Published online on: April 1, 2005     https://doi.org/10.3892/ijmm.15.4.641
  • Pages: 641-647
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Abstract

The most undesirable complication of an effective immunosuppressive therapy is neoplastic tumor recurrence or the development of de novo cancer. Though the immunosuppressive drug, mycophenolate mofetil (MMF), has been introduced into clinical practice, no data dealing with the influence of MMF on tumor cell malignancy are available. We analyzed the adhesion capacity of colon, pancreas and kidney carcinoma cell lines to endothelium, as well as their chemokine profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1, 1, and 10 µM MMF and compared to unstimulated controls. Chemokine analysis concentrated on the CXC family, including 6 CXC-receptors (CXCR) and 15 CXC-ligands (CXCL), and was carried out by reverse transcriptase-polymerase chain reaction and flow cytometry. MMF strongly diminished the adhesion capacity of HT-29 colon tumor cells but not of DanG pancreas tumor cells to endothelium. MMF also had a strong impact on the chemokine profile of colon, kidney and pancreas carcinomas, whereby individual changes were observed, depending on the tumor type. Down-regulating effects on chemokines did not correlate with down-regulating effects on tumor cell adhesion. Since several of the chemokines investigated are regulatory elements in the process of cell transformation, dissemination and angiogenesis, we speculate that MMF might prevent post-transplant tumor recurrence and transendothelial migration. However, the efficacy of MMF might differ according to the tumor type.

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April 2005
Volume 15 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Engl T, Relja B, Natsheh I, Makarevic J, Müller I, Beecken W, Jonas D and Blaheta RA: Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil. Int J Mol Med 15: 641-647, 2005
APA
Engl, T., Relja, B., Natsheh, I., Makarevic, J., Müller, I., Beecken, W. ... Blaheta, R.A. (2005). Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil. International Journal of Molecular Medicine, 15, 641-647. https://doi.org/10.3892/ijmm.15.4.641
MLA
Engl, T., Relja, B., Natsheh, I., Makarevic, J., Müller, I., Beecken, W., Jonas, D., Blaheta, R. A."Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil". International Journal of Molecular Medicine 15.4 (2005): 641-647.
Chicago
Engl, T., Relja, B., Natsheh, I., Makarevic, J., Müller, I., Beecken, W., Jonas, D., Blaheta, R. A."Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil". International Journal of Molecular Medicine 15, no. 4 (2005): 641-647. https://doi.org/10.3892/ijmm.15.4.641