title: Mesenchymal traits are selected along with stem features in breast cancer cells grown as mammospheres.
abstract: Increasing evidence indicates that invasive properties of breast cancers rely on gain of mesenchymal and stem features, which has suggested that the dual targeting of these phenotypes may represent an appealing therapeutic strategy. It is known that the fraction of stem cells can be enriched by culturing breast cancer cells as mammospheres (MS), but whether these pro-stem conditions favor also the expansion of cells provided of mesenchymal features is still undefined. In the attempt to shed light on this issue, we compared the phenotypes of a panel of 10 breast cancer cell lines representative of distinct subtypes (luminal, HER2-positive, basal-like and claudin-low), grown in adherent conditions and as mammospheres. Under MS-proficient conditions, the increment in the fraction of stem-like cells was associated to upregulation of the mesenchymal marker Vimentin and downregulation of the epithelial markers expressed by luminal cells (E-cadherin, KRT18, KRT19, ESR1). Luminal cells tended also to upregulate the myoepithelial marker CD10. Taken together, our data indicate that MS-proficient conditions do favor mesenchymal/myoepithelial features, and indicate that the use of mammospheres as an in vitro tumor model may efficiently allow the exploitation of therapeutic approaches aimed at targeting aggressive tumors that have undergone epithelial-to-mesenchymal transition
authors.affiliation: Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, Pordenone, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Borgna
authors.forename: Michela
authors.initials: M
authors.lastname: Armellin
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Gennaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestro
authors.forename: Manuela
authors.initials: M
authors.lastname: Santarosa
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor; D015820:Cadherins; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases; D050697:Retinal Dehydrogenase; D014746:Vimentin; C510223:ALDH1A1 protein, human