A new application note from AMSBIO, previously presented at both the 2014 Beatson International Cancer conference and the ELRIG Drug Discovery 2014 meeting in Manchester UK, introduces a more predictive and realistic model for early stage drug screening of cancer therapeutics.

The report 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.

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. 

In the new application report, a novel 3D spheroid triculture model for evaluating breast cancer progression is described.  In this model three different cell types are cultured together: a breast cancer cell line, together with human umbilical vein endothelial cells [HUVECs] and human adipose-derived mesenchymal stem cells [hMSCs] as an in vitro model for breast cancers in drug screening studies.

The proper physiology for each of these cell types is promoted using extracellular matrix proteins; and their activities and interactions assessed. The report demonstrates 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.

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