Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinoma.
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.
Gutwein
Paul
P
Pharmazentrum frankfurt/ZAFES, Klinikum der, Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. p.gutwein@med.uni-frankfurt.de
Schramme
Anja
A
Voss
Beren
B
Abdel-Bakky
Mohamed Sadek
MS
Doberstein
Kai
K
Ludwig
Andreas
A
Altevogt
Peter
P
Hansmann
Martin-Leo
ML
Moch
Holger
H
Kristiansen
Glen
G
Pfeilschifter
Josef
J
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
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