Ephrin-B1 Is a Novel Biomarker of Bladder Cancer Aggressiveness. Studies in Murine Models and in Human Samples
| Autor: | Mónica H. Vazquez-Levin, Denise Belgorosky, Marina Rosso, Juan Carlos Tejerizo, Silvia Vanzulli, Maria Ercilia Zubieta, Mariana Isola, Matías Ignacio González, Ana María Eiján, María Victoria Mencucci, María José Besso, Catalina Lodillinsky, Lara Lapyckyj |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
BIOMARKER
0301 basic medicine Cancer Research EPHRIN-B1 Receptor expression Ephrin-B1 lcsh:RC254-282 BETA-CATENIN CDH1 purl.org/becyt/ford/1 [https] 03 medical and health sciences 0302 clinical medicine medicine epithelial cadherin purl.org/becyt/ford/1.6 [https] Original Research Bladder cancer biology Cadherin Cancer beta-catenin Transfection BLADDER CANCER medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Cancer research biology.protein Immunohistochemistry bladder cancer biomarker sense organs EPITHELIAL CADHERIN |
| Zdroj: | Frontiers in Oncology, Vol 10 (2020) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Frontiers in Oncology |
| Popis: | Bladder cancer (BC) is the ninth most common cancer worldwide, but molecular changes are still under study. During tumor progression, Epithelial cadherin (E-cadherin) expression is altered and β-catenin may be translocated to the nucleus, where it acts as co-transcription factor of tumor invasion associated genes. This investigation further characterizes E-cadherin and β-catenin associated changes in BC, by combining bioinformatics, an experimental murine cell model (MB49/MB49-I) and human BC samples. In in silico studies, a DisGeNET (gene-disease associations database) analysis identified CDH1 (E-cadherin gene) as one with highest score among 130 BC related-genes. COSMIC mutation analysis revealed CDH1 low mutations rates. Compared to MB49 control BC cells, MB49-I invasive cells showed decreased E-cadherin expression, E- to P-cadherin switch, higher β-catenin nuclear signal and lower cytoplasmic p-Ser33-β-catenin signal, higher Ephrin-B1 ligand and EphB2 receptor expression, higher Phospho-Stat3 and Urokinase-type Plasminogen Activator (UPA), and UPA receptor expression. MB49-I cells transfected with Ephrin-B1 siRNA showed lower migratory and invasive capacity than control cells (scramble siRNA). By immunohistochemistry, orthotopic MB49-I tumors had lower E-cadherin, increased nuclear β-catenin, lower pSer33-β-catenin cytoplasmic signal, and higher Ephrin-B1 expression than MB49 tumors. Similar changes were found in human BC tumors, and 83% of infiltrating tumors depicted a high Ephrin-B1 stain. An association between higher Ephrin-B1 expression and higher stage and tumor grade was found. No association was found between abnormal E-cadherin signal, Ephrin-B1 expression or clinical-pathological parameter. This study thoroughly analyzed E-cadherin and associated changes in BC, and reports Ephrin-B1 as a new marker of tumor aggressiveness. Fil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Belgorosky, Denise. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Isola, Mariana. Hospital Italiano; Argentina Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Eiján, Ana María. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Tejerizo, Juan Carlos. Hospital Italiano; Argentina Fil: González, Matías Ignacio. Hospital Italiano; Argentina Fil: Zubieta, María Ercilia. Hospital Italiano; Argentina Fil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina |
| Databáze: | OpenAIRE |
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