title: Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells.
abstract: Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with tumor initiation and metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to cancer cells, whereas visceral adipose-derived stem cells incline to be "epithelial"-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of breast cancer cells by cell-cell contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs affect the low malignant breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell lymphoma and breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of breast cancer cells and render them resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727.
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritter
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Friemel
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Friderike
authors.initials: F
authors.lastname: Fornoff
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Mouhib
authors.initials: M
authors.lastname: Adjan
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Louwen
mesh_terms: D000328:Adult; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D050152:Intra-Abdominal Fat / Q000166:cytology*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000166:cytology*
keywords: adipose-derived stem cells; breast cancer cells; drug resistance; epithelial-to-mesenchymal transition; invasion