Pesticide exposure induces mammospheres formation and proangiogenic factors expression in breast cancer cells HER2 positive

ZARATE LORENA; NICOLA CANDIA AJ; MIRET NOELIA; ASAD AS; PONTILLO CA; CEBALLOS LEANDRO; CHIAPPINI FLORENCIA; CANDOLFI M; RANDI ANDREA

Congreso; Reunión Anual de Sociedades de Biociencias 2020; 2020

Sociedad Argentina de Investigación Clínica

Exposure to environmental pollutants, such as pesticides, has gained importance as a risk factor forbreast cancer, the leading cause of death by cancer in women. We have previously demonstratedthat the pesticide Hexachlorobenzene (HCB) stimulates breast cancer progression, facilitating cellmigration, invasion, tumor growth, angiogenesis and metastasis. HCB is a weak ligand for the ArylHydrocarbon Receptor (AhR), a ligand-activated transcription factor related to tumor and vasculardevelopment. Stem cells are of great interest due to their ability to originate, maintain and expandtumors, as well as to lead to metastasis and recurrences. Vascular endothelial growth factor (VEGF)and cyclooxygenase-2 (COX-2) are associated with tumor angiogenesis. The aim of this work is toexamine the HCB action on the capacity to mammospheres formation, expression of VEGF and COX2, production of interleukin-10 (IL-10), and to determine if the AhR pathway is involved in the effectsof HCB on tumor cell proliferation and migration. To this end, we used a Human Epidermal GrowthFactor Receptor 2 (HER2) positive murine breast cancer cell line, LM3, incubated with HCB in thepresence or absence of AhR inhibitors. Environmentally relevant HCB doses were used (0.005-5 μM).HCB stimulated the development of mammospheres at all doses tested (p