Our 3D Triculture Model for Evaluating Breast Cancer Progression (developed from technology used in our
spheroid assays) is part of a project to
demonstrate feasibility for an advanced drug screening platform.
The model shows that incorporating vascular and stromal cells with breast cancer tumor spheroids allows them to more closely mimic the extracellular environment, cellular architecture and behaviour of actual tumors; this
triculture promotes growth, invasion and endothelial recruitment.Three different cell types are cultured together:
- Breast cancer cell line (MCF7 or MDA-MB-231)
- Human umbilical vein endothelial cells (HUVECs)
- Human adipose-derived mesenchymal stem cells (hMSCs)
The proper physiology for each cell type is promoted using extracellular matrix proteins; and their activities and interactions assessed: demonstrating that in this triculture system, breast cancer MCTS exhibit cell-cell interactions with endothelial tubules and stromal cells, and there is an increase in both cell proliferation and invasion over the standard spheroid monoculture model.
TriCulture Application Note
TriCulture White Paper
Spheroid Assay Presentation:
Technology Highlight: Cultural Enrichment: Directing Cell Activities by Controlling Their Microenvironment
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Formation of tri-culture structure over 10 days.Red: breast cancer cell line (MDA-MB-231), Green: human umbilical vein endothelial cells (HUVECs); Blue: human adipose-derived mesenchymal stem cells (hMSCs).
Current 2D models for evaluating breast cancer progression do not provide a comprehensive, physiological approach to modeling the complex tumor microenvironment. 3D Tumor spheroids mark a significant advance over such 2D models in mimicking tumor physiology: like tumors, spheroid cultures exhibit cell-cell bond formation, comparable morphology, elevated cell survival and proliferation in their outer layers; while in the inner layers, they have reduced proliferation rates and a hypoxic core.
But while such Multi-Cellular Tumor Spheroids (MCTS) do provide a more physiological tumor model than 2D, other cell types are also essential for tumor behavior and cancer progression. Tissue vasculature provides a critical component, given the metabolic requirements of a growing tumor and known tumor-vascular interactions: so incorporating endothelial tubules with the MCTS adds interactions between vascular networks and growing tumors to the model. At the same time, stromal cells promote cell proliferation, dissemination, and drug resistance during cancer development.