Altered expression of β1 integrins in renal carcinoma cell lines exposed to the differentiation inducer valproic acid

  • Authors:
    • Anton Oertl
    • Borna Relja
    • Jasmina Makarevic
    • Eva Weich
    • Sonja Höfler
    • Jon Jones
    • Dietger Jonas
    • Hansjürgen Bratzke
    • Patrick C. Baer
    • Roman A. Blaheta
  • View Affiliations

  • Published online on: August 1, 2006     https://doi.org/10.3892/ijmm.18.2.347
  • Pages: 347-354
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Abstract

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Adhesion receptors of the β1 integrin family are assumed to be involved in carcinogenesis, but it is not clear how they contribute to RCC progression. In an in vitro model, we evaluated growth and adhesion capacity of Caki-I and KTC-26 kidney carcinoma cell lines compared to normal renal proximal tubular epithelial cells (PTC). α1-α6β1 integrin subunits in malignant and non-malignant cells were evaluated by Western blotting and RT-PCR, integrin surface expression was measured by flow cytometry and confocal microscopy. Additionally, tumor cells were allowed to re-differentiate in the presence of valproic acid (VPA) and dynamic alterations of the integrin profile were analyzed. Caki-I and KTC-26 were characterized by accelerated proliferation and adhesion to an endothelial cell monolayer, compared to PTC cells. The integrin β1 repertoire in RCC cell lines was significantly different from that detected in PTC, and included down-regulated α2 and α6, but up-regulated α1, α3 and α5 proteins. VPA application reduced tumor malignancy which was evidenced by reduced cell growth and adhesion capacity. The reduction in tumor malignancy was paralleled by the integrin expression profile of renal tumor cells ‘matching’ the pattern seen in PTC. We assume that a sensitive integrin balance exists in normal renal epithelial cells, and that dysregulation of the ‘physiological’ receptor equipment drives these cells towards malignancy. VPA acted on all investigated integrin subtypes and restored the receptor pattern typical for non-malignant cells. Therefore, VPA may represent a novel therapeutic option in RCC treatment.

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August 2006
Volume 18 Issue 2

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

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Spandidos Publications style
Oertl A, Relja B, Makarevic J, Weich E, Höfler S, Jones J, Jonas D, Bratzke H, Baer PC, Blaheta RA, Blaheta RA, et al: Altered expression of β1 integrins in renal carcinoma cell lines exposed to the differentiation inducer valproic acid. Int J Mol Med 18: 347-354, 2006
APA
Oertl, A., Relja, B., Makarevic, J., Weich, E., Höfler, S., Jones, J. ... Blaheta, R.A. (2006). Altered expression of β1 integrins in renal carcinoma cell lines exposed to the differentiation inducer valproic acid. International Journal of Molecular Medicine, 18, 347-354. https://doi.org/10.3892/ijmm.18.2.347
MLA
Oertl, A., Relja, B., Makarevic, J., Weich, E., Höfler, S., Jones, J., Jonas, D., Bratzke, H., Baer, P. C., Blaheta, R. A."Altered expression of β1 integrins in renal carcinoma cell lines exposed to the differentiation inducer valproic acid". International Journal of Molecular Medicine 18.2 (2006): 347-354.
Chicago
Oertl, A., Relja, B., Makarevic, J., Weich, E., Höfler, S., Jones, J., Jonas, D., Bratzke, H., Baer, P. C., Blaheta, R. A."Altered expression of β1 integrins in renal carcinoma cell lines exposed to the differentiation inducer valproic acid". International Journal of Molecular Medicine 18, no. 2 (2006): 347-354. https://doi.org/10.3892/ijmm.18.2.347