title: Breast cancer cells and bone marrow mesenchymal stromal cells: a regulated modulation of the breast tumor in the context of immune response.
abstract: OBJECTIVE
  The role of direct cell-cell interactions mediating selective bone metastasis by breast cancer cells (BCCs) niche is still mostly unknown.
  
  
  METHODS
  Conditioned medium and direct cell-cell contacts experiments were used to investigate the effect of bone marrow-derived mesenchymal stromal cells (MSCs), osteoprogenitor-like cells (MG-63) and osteosarcoma cells (SaOS-2) on luminal-like (MCF-7) and basal-like (MDA-MB-231) BCCs flow cytometry was used to assess the purity of isolated BCCs and osteoblasts. Expression of osteoblastic markers was investigated by semi-quantitative RT-PCR. RANKL and OPG levels were measured by ELISA.
  
  
  RESULTS
  Conditioned medium from MSCs and osteoblasts induced the expression of osteoblastic markers in BCCs. While co-culture assays with SaOS-2 increased the expression of osteoblastic markers in MCF-7 cells, SaOS-2 cell conditioned medium increased the expression of RANKL, PTHrP, VEGF and NOGGIN in MCF-7 cells. Co-cultures with either MG-63 cells or MSCs induced OPG and MMP-2 in both tumor cell lines. Interestingly, conditioned medium from co-cultures of MSCs and MDA-MB-231 cells significantly decreased the proliferation of activated T lymphocytes which was reversed by addition of anti-OPG antibodies to the co-cultures.
  
  
  CONCLUSIONS
  Our data suggest that MSCs strongly contribute to the adaptation and invasiveness of breast cancer cells in skeletal tissues.
authors: Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Campus Erasme, Bâtiment de Transfusion (Level +1), Route de Lennik no 808, 1070, Brussels, Belgium.
authors: Mehdi
authors: M
authors: Najar
authors: Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon.
authors: Hussein
authors: H
authors: Fayyad-Kazan
authors: School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon. wissam.faour@lau.edu.lb.
authors: Wissam H
authors: WH
authors: Faour
authors: Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon.
authors: Bassam
authors: B
authors: Badran
authors: Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Campus Erasme, Bâtiment de Transfusion (Level +1), Route de Lennik no 808, 1070, Brussels, Belgium.
authors: Fabrice
authors: F
authors: Journe
authors: Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Campus Erasme, Bâtiment de Transfusion (Level +1), Route de Lennik no 808, 1070, Brussels, Belgium.
authors: Laurence
authors: L
authors: Lagneaux
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: Bone metastasis; Breast cancer cells; Mesenchymal stromal cells; Osteoprogenitor cells