Table 1.
In vitro models for studying dormancy.
| Type | Used to study | Description | Reference |
|---|---|---|---|
| 2D culture/ECM | Dormant cancer cells | Tissue engineering scaffolds made of poly (ε-caprolactone) (PCL). Key features are random and aligned fibers that mimic tumor ECM. Seeding on the scaffold induced dormancy and stemness (Oct-4, Sox-2). | Guiro et al. [2015] |
| 2D culture/ECM | Dormant cancer cells | 2D clonogenic model of ER sensitive metastatic breast cancer cells in bone marrow. Cells form dormant colonies in the presence of FGF-2 on fibronectin-coated plates. | Tivari et al. [2015] |
| 3D coculture/ECM | Bone metastasis | Coculture system of breast cancer cells with bone marrow stromal cells (osteoblasts, mesenchymal cells, and endothelial cells) in 3D-collagen biomatrix. Dormancy is promoted by interaction of osteoblasts and mesenchymal bone marrow cells. | Marlow et al. [2013] |
| 3D coculture/ECM | Dormant ovarian cancer cells | Multilayer culture system of human ovarian cancer with fibroblasts, mesothelial cells and ECM (fibronectin, collagen). Mimics the bidirectional interaction of tumor cells, stromal cells and ECM. | [Kenny et al. 2015] |
| 3D coculture | Liver metastasis | Organoid culture system of metastatic breast cancer cells with fresh human primary hepatocytes and nonparenchymal cells. Mimics the hepatic microenvironment and allows for spontaneous breast cancer cell entry into dormancy. | Wheeler et al. [2014] |
| 3D ECM | Dormant breast/bone cancer cells | Highly metastatic cells [D2A1 (murine mammary), MDA-MB-231 (human breast), K7M2 (murine osteosarcoma)] cultured on a 3D basement membrane extract (BME) remain dormant for a few days followed by reactivation and proliferation. Can potentially be utilized to identify inhibitors of reactivation. | Barkan and Green [2011] |
| Microvascular niche | Bone metastasis | Organotypic models of microvascular niche in bone marrow and lung. Coculturing of HUVECs (human umbilical vein endothelial cells) and fibroblasts forms a microenvironment that induces cancer cell quiescence. | Ghajar et al. [2013]; Ghajar [2015] |
| Microvascular/bone niche | Bone metastasis | Coculture system of endothelial cells and mesenchymal stem cells potentiates vasculogenesis and osteogenesis forming a premetastatic bone niche for prostate cancer cells. | Chong et al. [2014] |
| Lung microenvironment | Lung metastasis | Ex vivo pulmonary metastasis assay in which cancer cells are tail-vein injected in mice and the excised lung slices with seeded single cells are maintained in culture medium to assess metastatic growth. Allows for real-time assessment of metastatic progression from single cells in the lung to multicellular colonies. | Mendoza et al. [2010] |
ECM, extracellular matrix; 2D, 2 dimensional; 3D, 3 dimensional; ER, estrogen receptor.