DE SIERVI Adriana
congresos y reuniones científicas
CtBP1 expression diminution on primary tumor impairs development of spontaneous lung metastases on a prostate cancer and metabolic syndrome model.
DALTON N; MASSILLO CL; PORRETTI J; SCALISE G; FARRÉ PL; DE LUCA P; DE SIERVI A
Mar del Plata
Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016
Sociedad Argentina de Investigación Clínica
Metabolic syndrome (MeS) increases prostate cancer (PCa) risk. C-Terminal Binding Protein (CtBP1) is a transcriptional corepressor that is activated by NADH binding. Previously our group established a MeS and PCa mice model that identified to CtBP1 as a novel link associating both diseases. We found that CtBP1 diminished the capability of PCa cell lines to adhere to a collagen matrix, repressing the epithelial marker CDH1 and inducing the mesenchymal marker VIM expressions. Death from PCa is not caused by the primary tumor, but rather the formation of metastasis; therefore, early diagnosis and prevention of metastasis in patients is of high relevance. Our aim was to investigate MeS/CtBP1 impact over PCa progression using an in vivo model of spontaneous PCa metastasis. NSG mice were fed with control or high fat diets during 12 weeks to induce MeS. Then PC3-CtBP1 depleted expression (PC3.shCtBP1) or -control (PC3.PGIPZ) cells were injected s.c. on MeS and control animals. Body weight and tumor size were measured 1 and 3 times a week, respectively. Thirty days after cell inoculation, tumors were around 1 cm , with no significant differences between treatments; however mice showed around 20% weight loss. Hence, mice were sacrificed and tumors, lungs and livers were collected for RNA isolation and histopathological analysis. Using human GAPDH specific primers in RT-qPCR from lungs, we found that CtBP1 depletion led to a dramatic decrease of lung metastases regardless of diet. In addition, H&E from lungs identified to PC3.shCtBP1/MeS group as the mice with the lowest metastatic lesions. Gene expression comparison between primary tumors and metastases showed that CtBP1 and cadherins mRNA levels were decreased in metastases. Our study uncovers for the first time the role of CtBP1 in PCa progression and its molecular targets in MeS mice.