Metabolomics of therapy resistance in an endocrine-related breast cancer mouse model

RITA ARAÚJO; VICTORIA FABRIS; ANA M. GIL; CAROLINE LAMB; LUISA HELGUERO; DANIELA BISPO; CLAUDIA LANARI

Conferencia; Small Molecule NMR Conference; 2019

Breast cancer (BC) is the most common and deadliest type of cancer in women. In most cases, breast tumors are hormone-dependent (HD) and rely on steroid hormones (estrogen and progesterone) to activate intracellular receptors and stimulate tumor growth. However, about 50% of the breast cancer patients in time develop resistance to antagonist therapy. This process involves the progression of HD tumors to hormone-independent tumors (HI) and ultimately to tumor resistance to therapy (HIR). The full mechanism and pathways involved in this progression process remain unknown. In this work, we applied an untargeted metabolomic strategy to characterize metabolic changes in the MPA (Medroxyprogesterone acetate) mouse mammary carcinoma model at different stages of tumor progression (HD, HI and HIR) [1-3]. Polar metabolites were extracted from tumor tissue samples and analyzed by 1H-NMR (500 MHz). The PCA and PLS-DA analysis showed robust separations between HD, HI and HIR tumors and PLS-DA loading plots helped to identify lower levels of glutamic acid, glutamine, glycine, taurine (among others) as characteristic of HI and HIR tumors, compared to HD. The observed distinguishing metabolic signatures of HD, HI and HIR tumors may be the basis for the definition of biomarkers of endocrine-related breast tumors at different stages of progression and will also provide information for future studies of metabolic pathways activated during BC progression.