Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins

• Autores: Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Melana Colavita, Juan Pablo; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Tumor Biology, 2016, vol. 37, no. 10, p. 1-13.
• Materia: Clear cell renal cell carcinoma (ccrcc); Erythropoietin (epo); Epo receptor (epo-r); Apoptosis; Stearoyl desaturase-1 (scd-1)
• Institución: Universidad Nacional del Nordeste

Fil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina.
Fil: Rodríguez, Juan Pablo. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina.
Fil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina.
Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina.
Fil: Todaro, Juan Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet – Nordeste; Argentina.
Fil: Espada, Joaquín Diego. Hospital Vidal. Departamento de Urología; Argentina.
Fil: Melana Colavita, Juan Pablo. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura; Argentina.
Fil: Melana Colavita, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina.
Fil: Brandan, Nora Cristina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina.
Fil: Brandan, Nora Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina.
Fil: Torres, Adriana Mónica. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina.
Fil: Aguirre, María Victoria. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina.
Fil: Aguirre, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxiainducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1(SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, BclxL, and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-xL overexpression was concomitant withtheenhancementofproliferativeindexes.SCD-1expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/ HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF1α, EPO, VEGF), their receptors (EPO-R, VEGFR-2), and SCD-1 in early stages of ccRCC.