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Title: Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells.
Authors: Morata-Tarifa, Cynthia
Jiménez, Gema
García, María A
Entrena, José M
Griñán-Lisón, Carmen
Aguilera, Margarita
Picon-Ruiz, Manuel
Marchal, Juan A
metadata.dc.contributor.authoraffiliation: [Morata-Tarifa,C; Jiménez,G; García,MA; Griñán-Lisón,C; Picon-Ruiz,M; Marchal,JA] Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain. [Morata-Tarifa,C; Jiménez,G; García,MA; Griñán-Lisón,C; Aguilera,M; Picon-Ruiz,M; Marchal,JA] Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain. [Jiménez,G; Marchal,JA] Department of Human Anatomy and Embryology, University of Granada, Granada, Spain. [García,MA] Department of Oncology, University Hospital Virgen de las Nieves, Granada, Spain. [Entrena,JM] Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain. Animal Behavior Research Unit, Scientific Instrumentation Center, University of Granada, Granada, Spain. [Aguilera,M] Department of Microbiology, University of Granada, Granada, Spain. [Picon-Ruiz,M] Braman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida, USA.
Keywords: Animales;Índice de masa corporal;Mama;Neoplasias de la mama;Cadherinas;Claudinas;Neoplasias del colon;Transición epitelial-mesenquimal;Xenoinjertos;Ratones;Recurrencia local de neoplasia;Células madre neoplásicas;Fenotipo;Tripsina;Caracoles;Regulación hacia arriba;Vimentina
metadata.dc.subject.mesh: Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzimidazoles
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index
Medical Subject Headings::Anatomy::Body Regions::Breast
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::Cadherins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Claudins
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colonic Neoplasms
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation::Epithelial-Mesenchymal Transition
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs
Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local
Medical Subject Headings::Anatomy::Cells::Stem Cells::Neoplastic Stem Cells
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
Medical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Mollusca::Gastropoda::Snails
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Serine Endopeptidases::Trypsin
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Vimentin
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Transplants::Heterografts
Issue Date: 11-Jan-2016
Publisher: Nature Publishing Group
Citation: Morata-Tarifa C, Jiménez G, García MA, Entrena JM, Griñán-Lisón C, Aguilera M, et al. Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells. Sci Rep. 2016; 6:18772
Abstract: Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.
Description: Journal Article;
metadata.dc.identifier.doi: 10.1038/srep18772
ISSN: 2045-2322 (Online)
Appears in Collections:01- Artículos - Complejo Hospitalario Universitario de Granada
01- Artículos - ibsGRANADA. Instituto de Investigación Biosanitaria de Granada

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