RESUMO
Dystroglycan (DG) is a cell surface receptor for extracellular matrix proteins and is involved in cell polarity, matrix organization, and mechanical stability of tissues. Previous studies documented loss of DG protein expression and glycosylation in a variety of cancer types, but the underlying mechanisms and the functional consequences with respect to cancer progression remain unclear. Here, we show that the level of expression of the ßDG subunit as well as the glycosylation status of the αDG subunit inversely correlate with the Gleason scores of prostate cancers; furthermore, we show that the functional glycosylation of αDG is substantially reduced in prostate cancer metastases. Additionally, we demonstrate that LARGE2 (GYLTL1B), a gene not previously implicated in cancer, regulates functional αDG glycosylation in prostate cancer cell lines; knockdown of LARGE2 resulted in hypoglycosylation of αDG and loss of its ability to bind laminin-111 while overexpression restored ligand binding and diminished growth and migration of an aggressive prostate cancer cell line. Finally, our analysis of LARGE2 expression in human cancer specimens reveals that LARGE2 is significantly down-regulated in the context of prostate cancer, and that its reduction correlates with disease progression. Our results describe a novel molecular mechanism to account for the commonly observed hypoglycosylation of αDG in prostate cancer.
Assuntos
Distroglicanas/genética , Distroglicanas/fisiologia , Regulação Neoplásica da Expressão Gênica , Glicosiltransferases/genética , Glicosiltransferases/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Neoplasias da Próstata/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Separação Celular , Progressão da Doença , Epitélio/metabolismo , Matriz Extracelular/metabolismo , Citometria de Fluxo , Glicosilação , Humanos , Imuno-Histoquímica/métodos , Laminina/metabolismo , Masculino , Microscopia de Fluorescência/métodos , Invasividade Neoplásica , RNA Interferente Pequeno/metabolismoRESUMO
Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammatory process that results in replacement of renal and/or perirenal tissue with a diffuse infiltrate of inflammatory cells referred to as xanthoma cells. We present a case of a 49-year-old man with an incidentally discovered renal mass with inferior vena cava (IVC) thrombus, who was found intraoperatively to have a significant inflammatory process involving the posterior wall of his IVC and right renal vein consistent with XGP surrounding a focus of clear cell renal cell carcinoma in the midportion of his right kidney.