Chloroquine Induces ROS-mediated Macrophage Migration Inhibitory Factor Secretion and Epithelial to Mesenchymal Transition in ER-positive Breast Cancer Cell Lines
| Autor: | Paola Maycotte, José Benito Montes-Alvarado, Julio Reyes-Leyva, Fabiola Lilí Sarmiento-Salinas, Nidia G. Pazos-Salazar, Eduardo Eleazar Jimenez-Ignacio, Alin García-Miranda, Verónica Vallejo-Ruiz, Israel Cotzomi-Ortega, Rubí Esmeralda Romo-Rodríguez, Guadalupe Rojas-Sanchez, Dalia Ramírez-Ramírez |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Epithelial-Mesenchymal Transition medicine.medical_treatment Estrogen receptor Breast Neoplasms Biology Cell Line Cell Line Tumor medicine Humans Secretion Epithelial–mesenchymal transition Macrophage Migration-Inhibitory Factors Autophagy Cancer Chloroquine medicine.disease Cadherins Cytokine Oncology Cancer cell Cancer research Macrophage migration inhibitory factor Female Reactive Oxygen Species Hydroxychloroquine |
| Zdroj: | Journal of mammary gland biology and neoplasia. 26(4) |
| ISSN: | 1573-7039 |
| Popis: | Breast cancer (BC) is the leading cause of cancer-related death in women in the world. Since tumor cells employ autophagy as a survival pathway, it has been proposed that autophagy inhibition could be beneficial for cancer treatment. There are several onging clinical trials where autophagy is being inhibited (using chloroquine, CQ or hydroxychloroquine, HCQ) along with chemotherapy with promising results. However, there is also in vitro evidence in which autophagy inhibition can induce epithelial to mesenchymal transition (EMT) in cancer cells, indicating that, at least in some cases, this strategy could be detrimental for cancer patients. In this study, we found that the genetic inhibition of autophagy primed cells for EMT by inducing a decrease in E-cadherin protein levels, while CQ treatment decreased E-cadherin levels, induced morphological changes related to EMT, increased EMT-related transcription factor (EMT-TF) expression and migration in estrogen receptor positive (ER +) BC cell lines. Importantly, CQ treatment increased intracellular reactive oxygen species (ROS) which induced the secretion of macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine related to malignancy. Both ROS production and MIF secretion were responsible for the mesenchymal morphology and increased migratory capacity induced by CQ. Our results indicate that CQ treatment increased malignancy by inducing ROS production, MIF secretion and EMT and suggest that autophagy inhibition in ER + BC patients might have detrimental effects. Our data indicates that a careful selection of patients should be performed in order to determine who will benefit the most from autophagy inhibition with available pharmacological agents for the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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