RUNX2 ABROGATES FGFR BLOCKADE IN HUMAN BREAST CANCER MODELS

LUTHY ISABEL A.; LAMB CAROLINE; PÉREZ CECILIA; RODRÍGUEZ MARÍA SOL; LANARI CLAUDIA

Congreso; Sociedad Argentina de Investigacion Clinica (SAIC); 2019

We have previously shown an interaction between the FGF2/FGFR2 axis and RUNX2 transcription factor. We have shown that FGFR2 or RUNX2 silencing in luminal IBH6 cells give rise to small tumors with a less aggressive phenotype and a lower proliferation index compared with control tumors. On the contrary, IBH6 or T47D cells overexpressing RUNX2 (RUNX2-IBH6 and RUNX2-T47D respectively) develop lung metastases and express high levels of FGFR2 and FGF2, showing a more aggressive phenotype than controls. This evidence supports the hypothesis that FGF2 increases RUNX2, and RUNX2 in turn increases FGF2 expression, maintaining a positive loop. The aim of this work was to evaluate if RUNX2 overexpressing tumors are sensitive to the FGFRs inhibitor PD173074.RESULTS: RUNX2-IBH6 or RUNX2-T47D cells and their respective controls (empty vector transfected cells) were injected into the flank of NSG mice. When the tumor size reached 30 mm2 animals were treated for 10 days with PD173074 (0,5 mg/day ip). Control treated tumors showed a significant inhibition of size (p