gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Loss of the „Coxsackie und Adenovirus Receptor (CAR)“ expression correlates with poor clinical outcome, tumor dedifferentiation, increased proliferation, and occurrence of distant metastasis in gastric adenocarcinomas

Meeting Abstract

  • corresponding author presenting/speaker Mario Anders - Laboratory for Angiogenesis and Tumor Metastasis, Charité, Campus Virchow-Klinikum, Berlin, Germany, Deutschland
  • Michael Vieth - University of Bayreuth, Institute of Pathology, Bayreuth, Germany
  • Annika Koschel - Laboratory for Angiogenesis and Tumor Metastasis, Charité, Campus Virchow-Klinikum, Berlin, Germany
  • Bertram Wiedenmann - Department of Internal Medicine, Divisions of Gastroenterology and Hepatology, Charite Medical School - Campus Virchow, Berlin, Germany
  • Christoph Röcken - Medizinische Fakultät der Otto-von-Guericke-Universität, Institute of Pathology, Magdeburg, Germany
  • Matthias Ebert - II. Medizinische Klinik, Klinikum rechts der Isar, TU München, München, Germany
  • Wolfgang Kemmner - Klinik für Chirurgie und Chirurgische Onkologie, Robert-Rössle-Klinik, Charité, Campus Buch, Max-Delbrück-Zentrum für Molekulare Medizin, Berlin
  • Michael Höcker - Laboratory for Angiogenesis and Tumor Metastasis, Charité, Campus Virchow-Klinikum, Berlin, Germany

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP170

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Veröffentlicht: 20. März 2006

© 2006 Anders et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Background: The Coxsackie and adenovirus receptor (CAR) represents a transmembrane component of epithelial tight junctions, being functionally linked to intercellular adhesion processes. Recent investigations suggest a role of CAR for the development of solid malignancies. The detailed function of CAR in the pathogenesis of cancer however, remains unclear. Therefore, we have investigated the abundance and distribution of CAR in normal and malignant gastric tissues and the potential impact of CAR on gastric cancer cell proliferation.

Material and Methods: CAR abundance and distribution were examined in samples of gastric cancer, non-transformed mucosa, and gastric cancer cell lines AGS, KATO III, MKN 28, and MKN 45 employing immunohistochemistry, immunofluorescence, confocal laser microscopy, RT-PCR, and Western blot analysis. Proliferation of AGS and MKN-45 cells was measured following ectopic CAR expression and after silencing CAR expression using specific siRNAs respectively.

Results: In 100% of the non-transformed gastric mucosa CAR was present at the basolateral and apical plasmamembrane of epithelial cells. In contrast only 57% of gastric cancer tissues displayed a positive CAR staining. The reduced CAR abundance in gastric cancer correlated significantly with low grades of tumor differentiation (p<0.0001), increased tumor size (p=0.001), and the occurrence of distant metastasis (p=0.0005). Moreover, loss of CAR was significantly associated with a poor clinical outcome (p=0.02). Among gastric cancer cell lines only AGS displayed considerable levels of CAR levelsin contrastto MKN28, KATOIII, and MNK45. Ectopic CAR expression in gastric carcinoma cells resulted in a significantly decreased proliferation, while inhibition of CAR by a specific siRNA yielded the opposite effect.

Conclusions: This study for the first time demonstrates the abundance and subcellular localization of CAR in the non-transformed and neoplastic gastric mucosa. Moreover, to our knowledge this is the first report linking this tight junction molecule to clinico-pathological parameters and the regulationof proliferation of gastric cancer cells. Taken together these findings suggest a relevant tumor biologic function of CAR in gastric cancer.