Elisabetta Bigagli1, Lorenzo Cinci2, Mario D'Ambrosio2, Cristina Luceri2. 1. Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section of Pharmacology and Toxicology, University of Florence, Florence, Italy elisabetta.bigagli@unifi.it. 2. Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.
Abstract
BACKGROUND/AIM: We examined the gene expression changes of breast cancer cells spontaneously undergoing epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) and the role of exosomes in these transitions. MATERIALS AND METHODS: Highly invasive mesenchymal-like breast cancer cells, MDA-MB-231 (basal cells), EMT and MET variants, were characterized by microarray gene expression profiling, immunocytochemistry and chemo-sensitivity. RESULTS: Spontaneously disseminated cells were anoikis resistant, exhibited a dissociative, EMT-like phenotype and underwent MET when reseeded in cell-free plates. MET was inhibited by exosomes secreted by basal cells. Chemo-sensitivity to doxorubicin, vincristine and paclitaxel decreased in the order EMT<MET<basal. Phenotypic plasticity arose with differential expression of metastasis and stemness associated genes (LGR5, FZD10, DTX1, ErbB3, FTH1 and DLL4) and pathways (DNA replication and repair, ABC transporter, Hedgehog, Notch and metabolic pathways). CONCLUSION: This is an appropriate model for studying EMT/MET transitions, drug targets and the role of exosomes in breast cancer dissemination. Copyright
BACKGROUND/AIM: We examined the gene expression changes of breast cancer cells spontaneously undergoing epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) and the role of exosomes in these transitions. MATERIALS AND METHODS: Highly invasive mesenchymal-like breast cancer cells, MDA-MB-231 (basal cells), EMT and MET variants, were characterized by microarray gene expression profiling, immunocytochemistry and chemo-sensitivity. RESULTS: Spontaneously disseminated cells were anoikis resistant, exhibited a dissociative, EMT-like phenotype and underwent MET when reseeded in cell-free plates. MET was inhibited by exosomes secreted by basal cells. Chemo-sensitivity to doxorubicin, vincristine and paclitaxel decreased in the order EMT<MET<basal. Phenotypic plasticity arose with differential expression of metastasis and stemness associated genes (LGR5, FZD10, DTX1, ErbB3, FTH1 and DLL4) and pathways (DNA replication and repair, ABC transporter, Hedgehog, Notch and metabolic pathways). CONCLUSION: This is an appropriate model for studying EMT/MET transitions, drug targets and the role of exosomes in breast cancer dissemination. Copyright