Metabolic syndrome increases CTBP1 expression and prostate cancer tumor growth in non-immunodeficient mice.

DALTON GN; MASSILLO C; PORRETTI J; SCALISE G; FARRÉ PL; DE LUCA P; DE SIERVI A

C.A.B.A.

Congreso; Reunión conjunta de sociedades de biociencias; 2017

Sociedad Argentina de Investigación Clínica

Abstract: Metabolic syndrome (MeS) is a patophysiological disorderthat increases prostate cancer (PCa) risk. C-Terminal BindingProtein (CtBP1), a transcriptional co-repressor of many tumor suppressorgenes, is considered a molecular metabolic sensor becauseit needs to bind NADH to become active. Previously, in our lab wehave established two mice models of MeS and PCa that allowedus to investigate CtBP1 role on tumor growth and progression fromlocalized to metastatic disease. Both models share the same flaw;tumors were generated on immunodeficient mice. Given the importanceof the immune system on all the aspects of cancer progressionand the association between, cancer, inflammation and obesity;our aim was to investigate the interaction between PCa andMeS on non-immunodeficient mice. We worked with male C57BL/6Jmice that were fed with control diet (CD) or high fat diet (HFD) by15 weeks. PCa TRAMP-C1 cells were injected subcutaneously inthe right flank of the animals. Tumor size was measured 3 times aweek during 30 days after inoculation. Animals were weighted oncea week along the whole experiment. After 10 weeks, HFD fed micewere significantly overweight compared to CD fed mice. These micealso showed higher glucose and cholesterol levels on serum samplescompared to CD fed mice. Regarding tumor growth, we founda significant increase in tumor volume on MeS group. Sixty daysafter cell inoculation we sacrificed the animals and collected tumors,lungs and liver tissue for RNA isolation and histopathological analysis.We found that tumors generated on HFD fed mice showed higherexpression of CtBP1 and lower expression of E-cadherin (CDH1),a known tumor suppressor and CtBP1 target. Histological analysisshowed no sign of micro- or macro-metastasis in soft tissues (thelungs and liver). Altogether, these results reinforced CtBP1 role asa crucial link that associates PCa development and MeS in miceindependently of immune system.