title: Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model.
abstract: Using an in vivo cycling strategy, we selected metastatic cancer cells from the lymph nodes (LN) of mice bearing orthotopic DU145 human prostate tumors. Repeated rounds of metastatic selection (LN1-LN4) progressively increased the epithelial phenotype, resulting in a new model of tumor cell mesenchymal-epithelial transition (MET). DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin. The MET in DU145-LN4 cells was accompanied by increased expression of the miR-200 family, and antimiRs to miR-200c and miR-141 induced an EMT. MET also correlated with the loss of miR-424. Ectopic transient and stable miR-424 expression induced EMT, with reduced epithelial marker expression and increased cell scattering. Our model provides evidence for spontaneous MET in vivo. We show that this cellular plasticity can be mediated through the combined action of miR-424 and the miR-200 family.
authors.affiliation: 1] Vascular Biology Program, Boston Children's Hospital, Karp Family Research Laboratories, 300 Longwood Ave., Boston, MA 02115 [2] Department of Surgery, Harvard Medical School, Boston, MA 02115.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Banyard
authors.forename: Ivy
authors.initials: I
authors.lastname: Chung
authors.forename: Arianne M
authors.initials: AM
authors.lastname: Wilson
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vetter
authors.forename: Antony
authors.initials: A
authors.lastname: Le Béchec
authors.forename: Diane R
authors.initials: DR
authors.lastname: Bielenberg
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Zetter
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014183:Transplantation, Heterologous; D014746:Vimentin / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015820:Cadherins; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D053538:Keratin-18; C583176:MIRN424 microRNA, mouse; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D016376:Oligonucleotides, Antisense; D014746:Vimentin