Guadalupe Rojas-Sanchez, Alin García-Miranda, José Benito Montes-Alvarado, Israel Cotzomi-Ortega, Fabiola Lilí Sarmiento-Salinas, Eduardo Eleazar Jimenez-Ignacio, Dalia Ramírez-Ramírez, Rubí Esmeralda Romo-Rodríguez, Julio Reyes-Leyva, Verónica Vallejo-Ruiz, Nidia Gary Pazos-Salazar, Paola Maycotte
{"title":"氯喹诱导雌激素受体阳性乳腺癌细胞ros介导的巨噬细胞迁移抑制因子分泌和上皮向间质转化","authors":"Guadalupe Rojas-Sanchez, Alin García-Miranda, José Benito Montes-Alvarado, Israel Cotzomi-Ortega, Fabiola Lilí Sarmiento-Salinas, Eduardo Eleazar Jimenez-Ignacio, Dalia Ramírez-Ramírez, Rubí Esmeralda Romo-Rodríguez, Julio Reyes-Leyva, Verónica Vallejo-Ruiz, Nidia Gary Pazos-Salazar, Paola Maycotte","doi":"10.1007/s10911-021-09503-5","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Chloroquine Induces ROS-mediated Macrophage Migration Inhibitory Factor Secretion and Epithelial to Mesenchymal Transition in ER-positive Breast Cancer Cell Lines.\",\"authors\":\"Guadalupe Rojas-Sanchez, Alin García-Miranda, José Benito Montes-Alvarado, Israel Cotzomi-Ortega, Fabiola Lilí Sarmiento-Salinas, Eduardo Eleazar Jimenez-Ignacio, Dalia Ramírez-Ramírez, Rubí Esmeralda Romo-Rodríguez, Julio Reyes-Leyva, Verónica Vallejo-Ruiz, Nidia Gary Pazos-Salazar, Paola Maycotte\",\"doi\":\"10.1007/s10911-021-09503-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":16413,\"journal\":{\"name\":\"Journal of Mammary Gland Biology and Neoplasia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2021-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Mammary Gland Biology and Neoplasia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10911-021-09503-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/11/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Mammary Gland Biology and Neoplasia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10911-021-09503-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/11/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Chloroquine Induces ROS-mediated Macrophage Migration Inhibitory Factor Secretion and Epithelial to Mesenchymal Transition in ER-positive Breast Cancer Cell Lines.
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.
期刊介绍:
Journal of Mammary Gland Biology and Neoplasia is the leading Journal in the field of mammary gland biology that provides researchers within and outside the field of mammary gland biology with an integrated source of information pertaining to the development, function, and pathology of the mammary gland and its function.
Commencing in 2015, the Journal will begin receiving and publishing a combination of reviews and original, peer-reviewed research. The Journal covers all topics related to the field of mammary gland biology, including mammary development, breast cancer biology, lactation, and milk composition and quality. The environmental, endocrine, nutritional, and molecular factors regulating these processes is covered, including from a comparative biology perspective.