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

BUJÁN, SOL; LEGUIZAMÓN, M. AGUSTINA; COCCA, CLAUDIA; MIRET, NOELIA; ZÁRATE, LORENA; PONTILLO, CAROLINA; CHIAPPINI, FLORENCIA; RANDI, ANDREA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2023; 2023

SAIC

Breast cancer is one of the leading cancers among women worldwide. Given the evidencethat pesticides play an important role in breast cancer, interest has grown in pesticide impacton disease progression. Organochlorine hexachlorobenzene (HCB) and organophosphatechlorpyrifos (CPF) are pesticides agonists of aryl hydrocarbon receptor (AhR), a transcriptionfactor involved in vascular development and tumor progression. Previously, we havereported that HCB and CPF exposure induced vascular endothelial growth factor (VEGF)secretion through AhR signaling in MDA-MB-231 breast cancer cells. VEGF binds to theVEGF?receptor 2 (VEGFR2) increasing endothelial proliferation, migration, andtubulogenesis. Our aim was to examine whether the conditioned media (CM) of MDA-MB231 tumor cells exposed to HCB or CPF are capable of activating EA.hy926 endothelialcells, promoting a) proliferation (PCNA levels by Western Blot), b) migration (wound healingassay), and c) tubulogenesis (tube-like structure formation in Matrigel assay). Besides, weanalyzed whether the effects are dependent on VEGFR2, using the ABYO inhibitor.Endothelial cells were exposed to 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. Results showed that CMfrom tumor cells exposed to HCB or CPF increased PCNA expression levels (55% and 87%,respectively; p