RESUMO
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.
Assuntos
Carcinoma de Células Renais/metabolismo , Moléculas de Adesão Celular/metabolismo , Transformação Celular Neoplásica/metabolismo , Regulação para Baixo , Imunoglobulinas/metabolismo , Neoplasias Renais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Técnicas de Silenciamento de Genes , Humanos , Imunoglobulinas/genética , Interferon gama/farmacologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Túbulos Renais Distais/metabolismo , Túbulos Renais Distais/patologia , RNA Interferente Pequeno/genética , Receptores de Superfície Celular , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
The aim of our study was to analyse the expression of CXCL16, ADAM10 and CXCR6 in renal cell carcinoma (RCC) tissue and to correlate the expression pattern with clinicopathologic data, including patient survival. Furthermore, we investigated CXCL16, ADAM10 and CXCR6 expressions by FACS, immunofluorescence and ELISA analysis in renal carcinoma cell lines. Our immunohistochemical analysis on tissue microarray of renal cancer samples of 104 patients revealed that ADAM10 correlated significantly with tumour stage, pathological nodal status, M status and lymphangiosis carcinomatosa. CXCL16, CXCR6 and ADAM10 were significantly increased in papillary carcinomas. Importantly, high levels of CXCL16 expression in renal cancer tissue correlated with better survival of patients, and CXCL16 correlated inversely to the tumour stage. In addition, inhibition of CXCL16 induced the migration of renal cancer cells assuming an anti-migratory function of transmembrane CXCL16. Taken together, our data demonstrate that downregulation of CXCL16 plays an important role in renal cancer development and progression, and that CXCL16 in RCC is an independent prognostic marker for better patient survival.