PESTICIDE EXPOSURE INDUCES MAMMOSPHERES FORMATION AND PROANGIOGENIC FACTORS EXPRESSION IN BREAST CANCER CELLS HER2 POSITIVE

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

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Fisiología y Sociedad Argentina de Inmunología

Exposure to environmental pollutants, such as pesticides, has gainedimportance as a risk factor for breast cancer, the leading cause of death bycancer in women. We have previously demonstrated that the pesticideHexachlorobenzene (HCB) stimulates breast cancer progression, facilitating cellmigration, invasion, tumor growth, angiogenesis and metastasis. HCB is a weakligand for the Aryl Hydrocarbon Receptor (AhR), a ligand-activatedtranscription factor related to tumor and vascular development. Stem cells areof great interest due to their ability to originate, maintain and expandtumors, as well as to lead to metastasis and recurrences. Vascular endothelialgrowth factor (VEGF) and cyclooxygenase-2 (COX-2) are associated with tumorangiogenesis. The aim of this work is to examine the HCB action on the capacityto mammospheres formation, expression of VEGF and COX-2, production ofinterleukin-10 (IL-10), and to determine if the AhR pathway is involved in theeffects of HCB on tumor cell proliferation and migration. To this end, we useda Human Epidermal Growth Factor Receptor 2 (HER2) positive murine breast cancercell line, LM3, incubated with HCB in the presence or absence of AhRinhibitors. Environmentally relevant HCB doses were used (0.005-5 μM). HCB stimulated the development ofmammospheres at all doses tested(p<0.01). In addition, HCB induced theprotein expression of VEGF and COX-2(p<0.05), favoring a proangiogenicenvironment. In a first approach to the immune compartment, the results showedthat HCB decreased intracellular levels of IL-10 (p<0.05). In addition, theexposure to the pesticide increased cell viability (p<0.05), proliferation(p<0.001) and migration (p<0.01) in these cells through an AhRpathway-dependent mechanism (p<0.01). These results suggest that HCBpromotes a dedifferentiated profile and the proangiogenic factors expression,contributing to tumor progression in a HER2breast cancer model.<!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073732485 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}size:595.0pt 842.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}