Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression
| Autor: | Santiago Ramón y Cajal, Eduard Sarró, Anna Meseguer, Enric Trilla, C. Mir, Jordi Vilardell, Nabil Ben Messaoud, Maria Rosa Vilà, J. López-Hellin, Emilio Itarte, Thais Cuadros, Juan Morote, Albert Blanco, Mayte Salcedo, Inés de Torres |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research Virus genetics Pathology medicine.medical_specialty Blotting Western Kaplan-Meier Estimate Kidney Hepatitis A Virus Cellular Receptor 1 Cell Line Tumor Biomarkers Tumor Humans Medicine Genetic Predisposition to Disease Carcinoma Renal Cell Aged Retrospective Studies Aged 80 and over Binding Sites Membrane Glycoproteins Tissue microarray business.industry Kidney metabolism Middle Aged Prognosis medicine.disease Immunohistochemistry Kidney Neoplasms Clear cell renal cell carcinoma HEK293 Cells medicine.anatomical_structure Microscopy Fluorescence Oncology Ectodomain Multivariate Analysis Mutation Disease Progression Receptors Virus Female business |
| Zdroj: | European Journal of Cancer. 49:2034-2047 |
| ISSN: | 0959-8049 |
| Popis: | Aim of the study To correlate hepatitis A virus cellular receptor (HAVCR)/kidney injury molecule-1 (KIM-1) expression in clear cell renal cell carcinoma (ccRCC) tumours with patient outcome and study the consequences of HAVCR/KIM-1 ectodomain shedding. Methods HAVCR/KIM-1 expression in ccRCC, oncocytomes, papillary carcinomas and unaffected tissue counterparts was evaluated. Minimal change disease and pre-clamping normal and ccRCC tissue biopsies were included. Tissue microarrays from 98 ccRCC tumours were analysed. Tumour registry data and patient outcome were retrospectivelly collected. Deletions in HAVCR/KIM-1 ectodomain and lentiviral infection of 786-O cells with HAVCR/KIM-1 mutated constructs to determine their subcellular distribution and invasive capacity were performed. Results HAVCR/KIM-1 was expressed in ccRCC, papillary tumours and in tubule cells of adjacent and distal unaffected counterparts of ccRCC tumours. The latest was not related to ischemic or tumour-related paracrine effects since pre-clamping normal biopsies were positive for HAVCR/KIM-1 and unaffected counterparts of papillary tumours were negative. HAVCR/KIM-1 analyses in patients and the invasive capacity of HAVCR/KIM-1 shedding mutants in cell lines demonstrated that: (i) relative low HAVCR/KIM-1 membrane levels correlate with activated shedding in ccRCC patients and mutant cell lines; (ii) augmented shedding directly correlates with higher invasiveness and tumour malignancy. Concluding statements Constitutive expression of HAVCR/KIM-1 in kidney might constitute a susceptibility trait for ccRCC tumour development. Enhanced HAVCR/KIM-1 ectodomain shedding promotes invasive phenotype in vitro and more aggressive tumours in vivo. |
| Databáze: | OpenAIRE |
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