title: Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinoma.
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-gamma and TNF-alpha 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.
authors.affiliation: Pharmazentrum frankfurt/ZAFES, Klinikum der, Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. p.gutwein@med.uni-frankfurt.de
authors.forename: Paul
authors.initials: P
authors.lastname: Gutwein
authors.forename: Anja
authors.initials: A
authors.lastname: Schramme
authors.forename: Beren
authors.initials: B
authors.lastname: Voss
authors.forename: Mohamed Sadek
authors.initials: MS
authors.lastname: Abdel-Bakky
authors.forename: Kai
authors.initials: K
authors.lastname: Doberstein
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D007136:Immunoglobulins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma