Hypoxic tumoral microenvironment and stearoyl-desaturase expression are associated with clear cell renal cell carcinoma survival and proliferation

STOYANOFF, TANIA; RODRÍGUEZ, JUAN PABLO; TODARO, JUAN; ESPADA, DIEGO; MELANA COLAVITA, JUAN PABLO; AGUIRRE, MARÍA VICTORIA

Mar del Plata

Congreso; XLVIII Reunión de Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2016

SAFE

Adapting to hypoxic stress is crucial in tumour progression and in determining its malignancy. The transcription factor for hypoxic adaptation (HIF-1α) is pivotal in modulating tumorous hypoxic responses. The most common of renal carcinomas is the clear cell adenocarcinoma (ccRCC) There is great interest to know the molecular basis of ccRCC tumor biology that might contribute to a better understanding of its aggressive biological behavior Thus, the aim of this study was to describe the relationship among the expression of HIF-1α, a key enzyme related to monounsaturated fatty acid synthesis, stearoyl desaturase-1 (SCD-1) and the angiogenic pair VEGF/VEGF-R2 in early stages of ccRCC. Tissue samples were obtained from patients at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina) who underwent radical nephrectomy for renal cancer. 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, 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, VEGF and VEGF-R2 were overexpressed in most samples. Bcl-xL enhancement was concomitant with the increment of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Particularly, data analysis reveals statistical positive correlations between SCD-1 and HIF-1 alfa (r2=0.97; p=0.0018), as well as, between SCD-1 and Ki-67 (r2=0.97; p=0.0018), suggesting a putative involvement of SCD-1 in tumor progression in early stages of ccRCC. This study provides new information of tumoral biology of ccRCC regarding to hypoxic microenvironment, lipogenesis and tumor cell proliferation that might contribute to propose SCD-1 as a biomarker and/or an oncotherapeutic target for this complex carcinoma.