1. Triple negative breast cancer cells exposed to aryl hydrocarbon receptor ligands hexachlorobenzene and chlorpyrifos activate endothelial cells.
- Author
-
Buján S, Pontillo C, Miret N, Leguizamón MA, Chiappini F, Cocca C, and Randi A
- Subjects
- Humans, Cell Line, Tumor, Ligands, Nitric Oxide Synthase Type II metabolism, Female, Endothelial Cells drug effects, Endothelial Cells metabolism, Cell Movement drug effects, Human Umbilical Vein Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells drug effects, Cell Proliferation drug effects, Chlorpyrifos toxicity, Receptors, Aryl Hydrocarbon metabolism, Hexachlorobenzene metabolism, Hexachlorobenzene toxicity, Vascular Endothelial Growth Factor A metabolism, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms pathology, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Cyclooxygenase 2 metabolism
- Abstract
Breast cancer is currently one of the most prevalent cancers worldwide. The mechanisms by which pesticides can increase breast cancer risk are multiple and complex. We have previously observed that two aryl hydrocarbon receptor (AhR) agonists ‒pesticides hexachlorobenzene (HCB) and chlorpyrifos (CPF)‒ act on tumor progression, stimulating cell migration and invasion in vitro and tumor growth in animal models. Elevated levels of hypoxia inducible factor-1α (HIF-1α) are found in malignant breast tumors, and HIF-1α is known to induce proangiogenic factors such as vascular endothelial growth factor (VEGF), nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2), which are fundamental in breast cancer progression. In this work, we studied HCB (0.005, 0.05, 0.5 and 5 μM) and CPF (0.05, 0.5, 5 and 50 μM) action on the expression of these proangiogenic factors in triple negative breast cancer cells MDA-MB-231, as well as the effect of their conditioned medium (CM) on endothelial cells. Exposure to pesticides increased HIF-1α and VEGF protein expression in an AhR-dependent manner. In addition, HCB and CPF boosted NOS-2 and COX-2 content and VEGF secretion in MDA-MB-231 cells. The treatment of endothelial cells with CM from tumor cells exposed to pesticides increased cell proliferation, migration, and tubule formation, enhancing both tubule length and branching points. Of note, these effects were VEGF-dependent, as they were blocked in the presence of a VEGF receptor-2 (VEGFR-2) inhibitor. In sum, our results highlight the harmful impact of HCB and CPF in modulating the interaction between breast cancer and endothelial cells and promoting angiogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF