title: Stromal Fibroblasts from the Interface Zone of Triple Negative Breast Carcinomas Induced Epithelial-Mesenchymal Transition and its Inhibition by Emodin.
abstract: "Triple negative breast cancer" (TNBC) is associated with a higher rate and earlier time of recurrence and worse prognosis after recurrence. In this study, we aimed to examine the crosstalk between fibroblasts and TNBC cells. The fibroblasts were isolated from TNBC patients' tissue in tumor burden zones, distal normal zones and interface zones. The fibroblasts were indicated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). Our study found that INFs grew significantly faster than NFs and CAFs in vitro. The epithelial BT20 cells cultured with the conditioned medium of INFs (INFs-CM) and CAFs (CAFs-CM) showed more spindle-like shape and cell scattering than cultured with the conditioned medium of NFs (NFs-CM). These results indicated that factors secreted by INFs-CM or CAFs-CM could induce the epithelial-mesenchymal transition (EMT) phenotype in BT20 cells. Using an in vitro co-culture model, INFs or CAFs induced EMT and promoted cancer cell migration in BT20 cells. Interestingly, we found that emodin inhibited INFs-CM or CAFs-CM-induced EMT programming and phenotype in BT20 cells. Previous studies reported that CAFs and INFs-secreted TGF-β promoted human breast cancer cell proliferation, here; our results indicated that TGF-β initiated EMT in BT20 cells. Pretreatment with emodin significantly suppressed the TGF-β-induced EMT and cell migration in BT20 cells. These results suggest that emodin may be used as a novel agent for the treatment of TNBC.
authors.affiliation: Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Hsiang-Chi
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Surgery, China Medical University Hospital, Taichung, Taiwan.|Department of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Liang-Chih
authors.initials: LC
authors.lastname: Liu
authors.affiliation: Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.|School of Medicine, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chao-Ming
authors.initials: CM
authors.lastname: Hung
authors.affiliation: Division of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taiwan.|School of Medicine, Tzu Chi University, Hualien, Taiwan.|Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey, United States of America.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
mesh_terms: D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004642:Emodin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D010641:Phenotype; D016212:Transforming Growth Factor beta / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016212:Transforming Growth Factor beta; D004642:Emodin