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

STOYANOFF, TANIA ROMINA; RODRIGUEZ, JUAN PABLO; TODARO, JUAN SANTIAGO; ESPADA, J. DIEGO; MELANA COLAVITA, JUAN PABLO; TORRES, ADRIANA MÓNICA; AGUIRRE, MARIA VICTORIA

Mar del Plata

Jornada; LXI ANNUAL MEETING ARGENTINE SOCIETY FOR CLINICAL INVESTIGATION (SAIC) - LXIV ANNUAL MEETING ARGENTINE SOCIETY OF IMMUNOLOGY (SAI) - XLVIII ANNUAL MEETING ARGENTINE SOCIETY OF EXPERIMENTAL PHARMACOLOGY (SAFE); 2016

SAFE - SAIC - SAI

Adapting to hypoxic stress is crucial in tumour progressionand in determining its malignancy. The transcription factor forhypoxic adaptation 􀀊H􀀫F􀀏􀀓α) is pivotal in modulating tumoroushypoxic responses. The most common of renal carcinomas isthe clear cell adenocarcinoma (ccRCC) There is great interestto 􀁍no􀁙 the molecular basis of cc􀀴CC tumor biology that mightcontribute to a better understanding of its aggressive biologicalbehaviour Thus, the aim of this study 􀁙as to describe the relationshipamong the expression of H􀀫F􀀏􀀓α, a 􀁍ey enzyme relatedto mono unsaturated fatty acid synthesis, stearoyl desaturase􀀏􀀓􀀊SC􀀦􀀏􀀓􀀋 and the angiogenic pair 􀀸E􀀩F/􀀸E􀀩F􀀏􀀴􀀔 in early stagesofcc􀀴CC. Tissue samples 􀁙ere obtained from patients at the􀀷rology 􀀷nit of the 􀀬.􀀴. 􀀸idal Hospital 􀀊Corrientes, Argentina􀀋􀁙ho under􀁙ent radical nephrectomy for renal cancer. Four experimentalgroups according to pathological stage and nucleargrade 􀁙ere organized􀀜 T􀀓􀀩􀀓􀀊n􀀟􀀘􀀋, T􀀔􀀩􀀓􀀊n􀀟􀀖􀀋, T􀀓􀀩􀀔􀀊n􀀟􀀙􀀋, andT􀀔􀀩􀀔􀀊n􀀟􀀙􀀋. The expression of H􀀫F􀀏􀀓α, 􀀸E􀀩F, 􀀸E􀀩F􀀴􀀏􀀔, 􀀤cl􀀏xLand SC􀀦􀀏􀀓 􀁙ere evaluated by immunohistochemistry, 􀀹esternblotting and/or 􀀴T􀀏􀀲C􀀴. Apoptosis 􀁙as assessed by the T􀀷-􀀰EL in situ assay and tumor proliferation 􀁙as determined by􀀭i􀀏􀀘􀀙 immunohistochemistry. 􀀦ata revealed that H􀀫F􀀏􀀓α, VEGFand 􀀸E􀀩F􀀏􀀴􀀔 􀁙ere overexpressed in most samples. 􀀤cl􀀏xLenhancement 􀁙as concomitant 􀁙ith the increment of proliferativeindexes. SC􀀦􀀏􀀓 expression increased 􀁙􀁙ith tthe ttuumoorr size and nu-􀀏clear grade. 􀀲articularly, data analysis reveals statistical po sitivecorrelations bet􀁙een SC􀀦􀀏􀀓 and H􀀫F􀀏􀀓 alfa 􀀊r2􀀟􀀒.􀀛􀀙􀀝 p􀀟􀀒.􀀒􀀒􀀓􀀚􀀋,as 􀁙ell as, bet􀁙een SC􀀦􀀏􀀓 and 􀀭i􀀏􀀘􀀙 􀀊r2􀀟􀀒.􀀛􀀙􀀝 p􀀟􀀒.􀀒􀀒􀀓􀀚􀀋, suggestinga putative involvement of SC􀀦􀀏􀀓 in tumor progressioninearly stages of cc􀀴CC. This study provides ne􀁙 information oftumoral biology of cc􀀴CC regarding to hypoxic microenvironment,lipogenesis and tumor cell proliferation that might contribute topropose SC􀀦􀀏􀀓 as a biomar􀁍er and/or an oncotherapeutic targetfor this complex carcinoma.