Loss of WISP2/CCN5 in estrogen-dependent MCF7 human breast cancer cells promotes a stem-like cell phenotype.
It has been proposed that the epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features. WISP2 (Wnt-1-induced signaling protein-2) plays an important role in maintenance of the differentiated phenotype of estrogen receptor-positive breast cancer cells and loss of WISP2 is associated with EMT. We now report that loss of WISP2 in MCF7 breast cancer cells can also promote the emergence of a cancer stem-like cell phenotype characterized by high expression of CD44, increased aldehyde dehydrogenase activity and mammosphere formation. Higher levels of the stem cell markers Nanog and Oct3/4 were observed in those mammospheres. In addition we show that low-cell inoculums are capable of tumor formation in the mammary fat pad of immunodeficient mice. Gene expression analysis show an enrichment of markers linked to stem cell function such as SOX9 and IGFBP7 which is linked to TGF-β inducible, SMAD3-dependent transcription. Taken together, our data demonstrate that WISP2 loss promotes both EMT and the stem-like cell phenotype.
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris, France ; Institut National de la Santé et de la Recherche Médicale, Paris, France ; Université Pierre et Marie Curie, Paris, France.
Nathalie
N
Ferrand
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris, France ; Institut National de la Santé et de la Recherche Médicale, Paris, France ; Université Pierre et Marie Curie, Paris, France.
Anne
A
Gnanapragasam
Immune system, Neuroinflammation and Neurodegenerative diseases, Centre de Recherche Saint-Antoine, Paris, France ; Institut National de la Santé et de la Recherche Médicale, Paris, France ; Université Pierre et Marie Curie, Paris, France.
Guillaume
G
Dorothee
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris, France ; Institut National de la Santé et de la Recherche Médicale, Paris, France ; Université Pierre et Marie Curie, Paris, France.
Gérard
G
Redeuilh
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris, France ; Institut National de la Santé et de la Recherche Médicale, Paris, France ; Université Pierre et Marie Curie, Paris, France.
Annette K
AK
Larsen
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris, France ; Institut National de la Santé et de la Recherche Médicale, Paris, France ; Université Pierre et Marie Curie, Paris, France.
Michèle
M
Sabbah
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D055511:CCN Intercellular Signaling Proteins; C413323:CCN5 protein, human; D004967:Estrogens; D018960:Hyaluronan Receptors; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta