Researchers at the University of Delaware have developed a dynamic 3D co-culture model for assessing the impact of microenvironment cues on ER+ breast cancer. The model is applicable for (T47D, ZR-75-1, BT474) dormancy, activation, or re-activation, including effects of bone marrow niche cells, specifically human mesenchymal stem cells (hMSCs) and bone lining human osteoblast cells (hFOBs). Studies have all been conducted in a biomimetic synthetic extracellular matrix with controlled biochemical content and mechanical properties. This approach addresses the needs for dissecting cell-cell and cell-matrix in ER+ breast cancer dormancy and has provided helpful insight into soluble secreted molecules that regulate dormancy and therapeutics approaches for targeting dormancy to promote continued cell proliferation or apoptosis.
Late recurrences of breast cancer at five or more years after successful treatment of the primary tumor most frequently occur in the bone marrow and for patients with estrogen receptor-positive (ER+) primary tumors. These late recurrences are hypothesized to arise from disseminated tumor cells (DTCs) that have reactivated after a long period of dormancy in the metastatic site. Robust model systems for probing DTC-microenvironment interactions are needed for mechanistic insights into this complex process and evaluation of therapeutics for preventing a late recurrence. Previously, no well-defined indirect co-culture 3D model had been established. Establishing this indirect, dynamic 3D co-culture model is very important for studying key secreted factors in absence of cell-cell contact to establish and evaluate new therapeutic targets.
· Provides the ability to screen the effects of secreted factors by niche cells
· Provides new insight into
o Soluble secreted molecules that regulate dormancy
o Therapeutics approaches for targeting dormancy
o Preventing late recurrence (inhibition of autophagy/key soluble factor signaling)
This newly developed technology is novel in its ability to provide indirect, dynamic 3D co-culture model that allows for the screening of effects of secreted factors (proteins, extracellular vesicles) by niche cells and related gene signatures that they induce in the breast cancer cells. This approach provides new tools for studying the activation of dormant breast cancer cells and screening of therapeutics for preventing a late recurrence, including inhibition of autophagy or key soluble factor signaling.
The technology is patent pending. Information on licensing opportunities is available on request.