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Tumor Biology

, Volume 37, Issue 10, pp 13581–13593 | Cite as

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

  • Tania Romina Stoyanoff
  • Juan Pablo Rodríguez
  • Juan Santiago Todaro
  • Joaquín Diego Espada
  • Juan Pablo Melana Colavita
  • Nora Cristina Brandan
  • Adriana Mónica Torres
  • María Victoria Aguirre
Original Article

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. 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 (hypoxia-inducible 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, Bcl-xL, 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 with the enhancement of proliferative indexes. SCD-1 expression 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 (HIF-1α, EPO, VEGF), their receptors (EPO-R, VEGFR-2), and SCD-1 in early stages of ccRCC.

Keywords

Clear cell renal cell carcinoma (ccRCC) Erythropoietin (EPO) EPO receptor (EPO-R) Apoptosis Stearoyl desaturase-1 (SCD-1) 

Notes

Acknowledgments

The authors thank to Dr. M.I. Delfino and the other pathologists of the Anatomopathology Unit of the J.R. Vidal Hospital of Corrientes (Argentina). This study was supported by the Grants: 2011-0212 PICTO UNNE (FONCyT- UNNE), PI 17/I008; PI 17/I010 and PI I004-2014 (SEGCyT, UNNE). Juan Pablo Melana Colavita is the recipient of a doctoral fellowship of CONICET-UNNE and Tania Romina Stoyanoff is the recipient of a postdoctoral fellowship of CONICET-UNNE.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Tania Romina Stoyanoff
    • 1
  • Juan Pablo Rodríguez
    • 1
  • Juan Santiago Todaro
    • 1
  • Joaquín Diego Espada
    • 2
  • Juan Pablo Melana Colavita
    • 1
  • Nora Cristina Brandan
    • 1
  • Adriana Mónica Torres
    • 3
  • María Victoria Aguirre
    • 1
  1. 1.Laboratory of Biochemical Investigations (LIBIM), Basic Medical Sciences Department, School of MedicineNational Northeastern University (UNNE), IQUIBA-CONICETCorrientesArgentina
  2. 2.Department of UrologyJ.R. Vidal HospitalCorrientesArgentina
  3. 3.Pharmacology, Faculty of Biochemical and Pharmaceutical SciencesNational University of Rosario (UNR), CONICETRosarioArgentina

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