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Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinoma |
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| Authors: | Paul Gutwein Anja Schramme Mohamed Sadek Abdel-Bakky Andreas Ludwig Martin-Leo Hansmann Glen Kristiansen Josef Pfeilschifter |
| Institution: | a Pharmazentrum frankfurt/ZAFES, Klinikum der, Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany b Institute of Pharmacology and Toxicology, University Hospital RWTH, Aachen, Germany c Tumor Immunology Programme, German Cancer Research Center, Heidelberg, Germany d Institute of Pathology, Goethe-Universität, Frankfurt am Main, Germany e Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland |
| Abstract: | Junctional adhesion molecule-A (JAM-A) is one component of tight junctions which are involved in important processes like paracellular permeability, cell polarity, adhesion, migration, and angiogenesis. Here we describe JAM-A expression in distal convoluted tubule, connecting tubule, and in cells of the collecting duct of the healthy human kidney. In addition, JAM-A was weakly expressed in cells of the proximal tubule. Using immunofluorescence, FACS and Western blot analysis we investigated JAM-A expression in tubular cells in vitro. Interestingly, treatment of HK-2 cells with IFN-γ and TNF-α resulted in a metalloproteinase mediated downregulation of JAM-A. Importantly, in a tissue micro-array JAM-A protein expression was significantly downregulated in patients with clear cell renal cell carcinoma. Furthermore, knockdown of JAM-A with JAM-A specific siRNA induced the migration of RCC4 cells. In summary, downregulation of JAM-A is an early event in the development of renal cancer and increases the migration of renal cancer cells. |
| Keywords: | JAM-A Kidney Renal cancer Metalloproteinases Tight junctions |
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