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

ZÁRATE, LORENA; ASAD, ANTONELLA; CHIAPPINI, FLORENCIA; NICOLA CANDI, ALEJANDRO; PONTILLO, CAROLINA; CANDOLFI, MARIANELA; MIRET, NOELIA; CEBALLOS, LEANDRO; RANDI, ANDREA

CABA

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2020; 2020

Sociedad Argentina de Investigación Clínica

Exposure to environmental pollutants, such as pesticides, has gained importance as a risk factor for breast cancer, the leading cause of death by cancer in women. We have previously demonstrated that the pesticide Hexachlorobenzene (HCB) stimulates breast cancer progression, facilitating cell migration, invasion, tumor growth, angiogenesis and metastasis. HCB is a weak ligand for the Aryl Hydrocarbon Receptor (AhR), a ligand-activated transcription factor related to tumor and vascular development. Stem cells are of great interest due to their ability to originate, maintain and expand tumors, 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 to examine the HCB action on the capacity to mammospheres formation, expression of VEGF and COX-2, production of interleukin-10 (IL-10), and to determine if the AhR pathway is involved in the effects of HCB on tumor cell proliferation and migration. To this end, we used a Human Epidermal Growth Factor Receptor 2 (HER2) positive murine breast cancer cell line, LM3, incubated with HCB in the presence 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