title: Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer.
abstract: Cancer-associated fibroblasts (CAF) comprise the majority of stromal cells in breast cancers, yet their precise origins and relative functional contributions to malignant progression remain uncertain. Local invasion leads to the proximity of cancer cells and adipocytes, which respond by phenotypical changes to generate fibroblast-like cells termed as adipocyte-derived fibroblasts (ADF) here. These cells exhibit enhanced secretion of fibronectin and collagen I, increased migratory/invasive abilities, and increased expression of the CAF marker FSP-1 but not α-SMA. Generation of the ADF phenotype depends on reactivation of the Wnt/β-catenin pathway in response to Wnt3a secreted by tumor cells. Tumor cells cocultivated with ADFs in two-dimensional or spheroid culture display increased invasive capabilities. In clinical specimens of breast cancer, we confirmed the presence of this new stromal subpopulation. By defining a new stromal cell population, our results offer new opportunities for stroma-targeted therapies in breast cancer.
authors.affiliation: Authors' Affiliations: Université de Toulouse, UPS; CNRS; Institut de Pharmacologie et de Biologie Structurale; Institut National de la Santé et de la Recherche Médicale, INSERM U1048; Institut Claudius Regaud, EA3035; and Service d'Anatomo-Pathologie, Hôpital de Rangueil, Toulouse, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Bochet
authors.forename: Camille
authors.initials: C
authors.lastname: Lehuédé
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dauvillier
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Wang
authors.forename: Béatrice
authors.initials: B
authors.lastname: Dirat
authors.forename: Victor
authors.initials: V
authors.lastname: Laurent
authors.forename: Cédric
authors.initials: C
authors.lastname: Dray
authors.forename: Romain
authors.initials: R
authors.lastname: Guiet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maridonneau-Parini
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Gonidec
authors.forename: Bettina
authors.initials: B
authors.lastname: Couderc
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Escourrou
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Catherine
authors.initials: C
authors.lastname: Muller
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D005353:Fibronectins; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin