title: A novel model of dormancy for bone metastatic breast cancer cells.
abstract: Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy.
authors.affiliation: Authors' Affiliations: Stem Cell Group, Breakthrough Breast Cancer Research Unit, Research Oncology, King's College London School of Medicine, Guy's Hospital; Department of Craniofacial Development and Stem Cell Biology, King's College London, Guy's Hospital; Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, United Kingdom; and Rutgers New Jersey Medical School, Newark, New Jersey.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Marlow
authors.forename: Gabriella
authors.initials: G
authors.lastname: Honeth
authors.forename: Sara
authors.initials: S
authors.lastname: Lombardi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cariati
authors.forename: Sonya
authors.initials: S
authors.lastname: Hessey
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pipili
authors.forename: Veronica
authors.initials: V
authors.lastname: Mariotti
authors.forename: Bharath
authors.initials: B
authors.lastname: Buchupalli
authors.forename: Katie
authors.initials: K
authors.lastname: Foster
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.forename: Agamemnon
authors.initials: A
authors.lastname: Grigoriadis
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
authors.forename: Anand
authors.initials: A
authors.lastname: Purushotham
authors.forename: Andrew
authors.initials: A
authors.lastname: Tutt
authors.forename: Gabriela
authors.initials: G
authors.lastname: Dontu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology*