title: Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells.
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.
authors.affiliation: Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain.|Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Morata-Tarifa
authors.affiliation: Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain.|Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.|Department of Human Anatomy and Embryology, University of Granada, Granada, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Jiménez
authors.affiliation: Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain.|Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.|Department of Oncology, University Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: García
authors.affiliation: Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.|Animal Behavior Research Unit, Scientific Instrumentation Center, University of Granada, Granada, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Entrena
authors.affiliation: Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain.|Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Griñán-Lisón
authors.affiliation: Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.|Department of Microbiology, University of Granada, Granada, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Aguilera
authors.affiliation: Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain.|Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.|Braman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Picon-Ruiz
authors.affiliation: Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain.|Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain.|Department of Human Anatomy and Embryology, University of Granada, Granada, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Marchal
mesh_terms: D000818:Animals; D015415:Biomarkers; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D058985:Side-Population Cells; D014410:Tumor Stem Cell Assay
chemical_list: D015415:Biomarkers