title: Mesenchymal Stem Cell-Derived Exosomes Stimulate Cycling Quiescence and Early Breast Cancer Dormancy in Bone Marrow.
abstract: Dormant breast cancers resurge as metastatic disease after a long dormancy period in the bone marrow, where cancer cells interact with mesenchymal stem cells (MSC). However, the nature of early interactions between breast cancer cells and MSCs in the bone marrow microenvironment that facilitate adaptation to a quiescent state remains poorly understood. Here, we report that breast cancer cells prime MSC to release exosomes containing distinct miRNA contents, such as miR-222/223, which in turn promotes quiescence in a subset of cancer cells and confers drug resistance. Building on these results, we developed a novel, nontoxic therapeutic strategy to target dormant breast cancer cells based on systemic administration of MSC loaded with antagomiR-222/223. In an immunodeficient mouse model of dormant breast cancer, this therapy sensitized breast cancer cells to carboplatin-based therapy and increased host survival. Overall, our findings illuminate the nature of the regulatory interactions between breast cancer cells and MSCs in the evolution of tumor dormancy and resurgence in the micrometastatic microenvironment of the bone marrow. Cancer Res; 76(19); 5832-44. ©2016 AACR.
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey. Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Sarah A
authors: SA
authors: Bliss
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey. Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Garima
authors: G
authors: Sinha
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Oleta A
authors: OA
authors: Sandiford
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey. Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Lisa M
authors: LM
authors: Williams
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey. Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Daniel J
authors: DJ
authors: Engelberth
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Khadidiatou
authors: K
authors: Guiro
authors: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Leidy L
authors: LL
authors: Isenalumhe
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Steven J
authors: SJ
authors: Greco
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Seda
authors: S
authors: Ayer
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Margarette
authors: M
authors: Bryan
authors: Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC.
authors: Rakesh
authors: R
authors: Kumar
authors: Department of Pathology and Laboratory Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
authors: Nicholas M
authors: NM
authors: Ponzio
authors: Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey. Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Newark, New Jersey. rameshwa@njms.rutgers.edu.
authors: Pranela
authors: P
authors: Rameshwar
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D016190:Carboplatin / Q000627:therapeutic use; D045744:Cell Line, Tumor; D055354:Exosomes / Q000502:physiology*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D016190:Carboplatin; D035683:MicroRNAs; C525710:MIR222, human; C525067:MIR223, human