title: The bone marrow niche in support of breast cancer dormancy.
abstract: Despite the success in detecting breast cancer (BC) early and, with aggressive therapeutic intervention, BC remains a clinical problem. The bone marrow (BM) is a favorable metastatic site for breast cancer cells (BCCs). In BM, the survival of BCCs is partly achieved by the supporting microenvironment, including the presence of immune suppressive cells such as mesenchymal stem cells (MSCs). The heterogeneity of BCCs brings up the question of how each subset interacts with the BM microenvironment. The cancer stem cells (CSCs) survive in the BM as cycling quiescence cells and, forming gap junctional intercellular communication (GJIC) with the hematopoietic supporting stromal cells and MSCs. This type of communication has been identified close to the endosteum. Additionally, dormancy can occur by soluble mediators such as cytokines and also by the exchange of exosomes. These latter mechanisms are reviewed in the context of metastasis of BC to the BM for transition as dormant cells. The article also discusses how immune cells such as macrophages and regulatory T-cells facilitate BC dormancy. The challenges of studying BC dormancy in 2-dimensional (2-D) system are also incorporated by proposing 3-D system by engineering methods to recapitulate the BM microenvironment.
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA; Graduate School of Biomedical Sciences at New Jersey Medical School, Newark, NJ, USA.
authors.forename: Nykia D
authors.initials: ND
authors.lastname: Walker
authors.affiliation: Graduate School of Biomedical Sciences at New Jersey Medical School, Newark, NJ, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Patel
authors.affiliation: Ob/Gyn and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jessian L
authors.initials: JL
authors.lastname: Munoz
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA; Graduate School of Biomedical Sciences at New Jersey Medical School, Newark, NJ, USA.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Hu
authors.affiliation: Graduate School of Biomedical Sciences at New Jersey Medical School, Newark, NJ, USA.
authors.forename: Khadidiatou
authors.initials: K
authors.lastname: Guiro
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA; Graduate School of Biomedical Sciences at New Jersey Medical School, Newark, NJ, USA.
authors.forename: Garima
authors.initials: G
authors.lastname: Sinha
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA; Graduate School of Biomedical Sciences at New Jersey Medical School, Newark, NJ, USA. Electronic address: rameshwa@njms.rutgers.edu.
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D049109:Cell Proliferation; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: Bone marrow; Breast cancer; Connexin; Cytokines; Dormancy; Gap junction