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Proteinase-activated receptor 2 (PAR2) in cholangiocarcinoma (CCA) cells: effects on signaling and cellular level

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Abstract

In this study, we demonstrate functional expression of the proteinase-activated receptor 2 (PAR2), a member of a G-protein receptor subfamily in primary cholangiocarcinoma (PCCA) cell cultures. Treatment of PCCA cells with the serine proteinase trypsin and the PAR2-selective activating peptide, furoyl-LIGRLO-NH2, increased migration across a collagen membrane barrier. This effect was inhibited by a PAR2-selective pepducin antagonist peptide (P2pal-18S) and it was also blocked with the Met receptor tyrosine kinase (Met) inhibitors SU 11274 and PHA 665752, the MAPKinase inhibitors PD 98059 and SL 327, and the Stat3 inhibitor Stattic. The involvement of Met, p42/p44 MAPKinases and Stat3 in PAR2-mediated PCCA cell signaling was further supported by the findings that trypsin and the PAR2-selective agonist peptide, 2-furoyl-LIGRLO-NH2, stimulated activating phosphorylation of these signaling molecules in cholangiocarcinoma cells. With our results, we provide a novel signal transduction module in cholangiocarcinoma cell migration involving PAR2-driven activation of Met, p42/p44 MAPKinases and Stat3.

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Acknowledgments

The authors would like to thank Beate Schulze and Elke Oswald, Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, and Frank Steiniger, Electron Microscopy Center, University Hospital Jena for the excellent technical assistance. This work was supported in part by German Cancer Aid (R.K., Project 108809).

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Authors and Affiliations

  1. Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Medical Faculty at the Friedrich Schiller University Jena, University Hospital Jena, Drackendorfer Str. 1, 07747, Jena, Germany

    Roland Kaufmann, Alexander Hascher & Franziska Mußbach

  2. Institute of Biochemistry, Charité, Humboldt University of Berlin, Oudenarder Str. 16, 13347, Berlin, Germany

    Petra Henklein

  3. Institute of Pathology, Medical Faculty at the Friedrich Schiller University Jena, Zieglemühlenweg 1, 07743, Jena, Germany

    Kathrin Katenkamp

  4. Electron Microscopy Center, Medical Faculty at the Friedrich Schiller University Jena, Ziegelmühlenweg 1, 07743 , Jena, Germany

    Martin Westermann

  5. Department of General, Visceral and Vascular Surgery, Erlanger Allee Allee 101, 07747, Jena, Germany

    Utz Settmacher

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  1. Roland Kaufmann
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  2. Alexander Hascher
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  3. Franziska Mußbach
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Correspondence to Roland Kaufmann.

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Kaufmann, R., Hascher, A., Mußbach, F. et al. Proteinase-activated receptor 2 (PAR2) in cholangiocarcinoma (CCA) cells: effects on signaling and cellular level. Histochem Cell Biol 138, 913–924 (2012). https://doi.org/10.1007/s00418-012-1006-4

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