ANGIOGENESIS IN BREAST CANCER: PESTICIDES ACTIVATE ENDOTHELIAL CELLS VIA VEGF RECEPTOR- 2 SIGNALING

BUJÁN SOL; PONTILLO CAROLINA ANDREA; MIRET NOELIA VICTORIA; LEGUIZAMÓN MARÍA AGUSTINA; CHIAPPINI FLORENCIA ANA; ZÁRATE LORENA; COCCA CLAUDIA; RANDI ANDREA SILVANA

Congreso; Reunión Anual de Sociedades de Biociencias 2023; 2023

Breast cancer is one of the leading cancers among women worldwide.Given the evidence that pesticides play an important role inbreast cancer, interest has grown in pesticide impact on diseaseprogression. Organochlorine hexachlorobenzene (HCB) and organophosphatechlorpyrifos (CPF) are pesticides agonists of arylhydrocarbon receptor (AhR), a transcription factor involved in vasculardevelopment and tumor progression. Previously, we have reportedthat HCB and CPF exposure induced vascular endothelial growthfactor (VEGF) secretion through AhR signaling in MDA-MB-231breast cancer cells. VEGF binds to the VEGF–receptor 2 (VEGFR2)increasing endothelial proliferation, migration, and tubulogenesis.Our aim was to examine whether the conditioned media (CM) ofMDA-MB- 231 tumor cells exposed to HCB or CPF are capableof activating EA.hy926 endothelial cells, promoting a) proliferation(PCNA levels by Western Blot), b) migration (wound healing assay),and c) tubulogenesis (tube-like structure formation in Matrigel assay).Besides, we analyzed whether the effects are dependent onVEGFR2, using the ABYO inhibitor. Endothelial cells were exposedto the CM of MDA-MB-231 cells treated to ethanol, HCB (0.05 μM)or CPF (0.05 μM), in the presence or absence of ABYO. Resultsshowed that CM from tumor cells exposed to HCB or CPF increasedPCNA expression levels (55% and 87%, respectively; p<0.05), indicatinggreater proliferation. Moreover, endothelial cells showed asignificant increase in migration in the presence of CM of HCB orCPF (32% and 28%, respectively; p<0.01; p<0.05). Finally, both CMof HCB and CPF promoted the formation of tubules, increasing thetotal tube length (60%, p<0.01) and branching points (44%, p<0.05).The CM effects on the biological functions analyzed depended onthe VEGFR2 pathway. In conclusion, the exposure to HCB and CPFpesticides stimulates angiogenesis processes, promoting breastcancer progression.