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New tools for assessing the individual risk of metastasis in renal cell carcinoma

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Abstract

Localized renal cell carcinoma (RCC) progresses to metastastic disease in 20–40 % after surgical resection. Affected patients might benefit from adjuvant treatment and have to be reliably identified for treatment indication. However, existing molecular markers and classification nomograms lack sufficient validity for clinical application so far. Therefore, in order to improve diagnostic tools for the identification of patients at risk, we tested invasiveness and the capability to activate vascular endothelium of primary RCC cells as tumor specific functional parameters. As a parameter for cell invasiveness the ability of RCC cells to break-down transepithelial electrical resistance (TEER) of an epithelial cell monolayer was tested. Loss of resistance, calculated as invasivity index, resembled the degree of cell invasiveness. In addition, secretion of Von Willebrand Factor by endothelial cells incubated with RCC cell supernatant was measured as a surrogate marker for endothelial cell activation. TEER-assay results matched clinical status of disease in 9 out of 12 cases. Metastatic tumors and less differentiated tumors had a significant increase of invasivity index (p = 0.007; p = 0.034). Endothelial cell activation and clinical outcome matched in 5 out of 9 samples. In addition, tumor cell induced endothelial cell activation significantly correlated to the pathologic T classification status of RCC tumors (p = 0.009). Taken together, our study validated endothelial cell activation analysis and cell invasiveness as solitary prognostic markers for tumor dissemination. TEER-analysis has proven to be a useful functional assay giving highly relevant individual information on functional tumor cell characteristics that add to pathologic evaluation.

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Abbreviations

C7:

Madin–Darby canine kidney cell line C7

CAIX:

Carbonic anhydrase IX

ECA:

Endothelial cell activation

HUVEC:

Human umbilical vein cells

MMP:

Matrix metalloproteinases

RCC:

Renal cell carcinoma

TEER:

Transepithelial electrical resistance

VWF:

Von Willebrand Factor

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Acknowledgments

This study was supported by a Grant of the Interdisciplinary Center of Clinical Research (IZKF) Münster, Germany (Goe2/023/10) and the research grant GO1360/4-1 by the Deutsche Forschungsgemeinschaft.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Urology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Building A1, Münster, Germany

    Edwin Herrmann, Gerald Pühse & Laura Maria Krabbe

  2. Department of Dermatology, University Hospital of Münster, Von Esmarch Straße 58, 48149, Münster, Germany

    Carsten Weishaupt, Birgit Pöppelmann, Carina Hillgruber, Micha Feld, Martin Steinhoff & Tobias Goerge

  3. Department of Dermatology, UCSF, San Francisco, CA, USA

    Martin Steinhoff

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  1. Edwin Herrmann
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  2. Carsten Weishaupt
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  9. Tobias Goerge
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Corresponding author

Correspondence to Tobias Goerge.

Additional information

Edwin Herrmann and Carsten Weishaupt contributed equally to this study.

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Herrmann, E., Weishaupt, C., Pöppelmann, B. et al. New tools for assessing the individual risk of metastasis in renal cell carcinoma. Clin Exp Metastasis 30, 215–224 (2013). https://doi.org/10.1007/s10585-012-9529-6

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  • DOI: https://doi.org/10.1007/s10585-012-9529-6

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