Engineered cancer in vitro model to demultiplex biophysical cues in metastasis

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Breast cancer is the most common cancer in women in the UK. Whilst prognosis for patients with low grade disease continually improves, 70% of patients with advanced breast cancer develop incurable bone metastases. The mechanisms driving targeted metastases are complex, requiring changes in both the primary tumour and the metastatic niche. A significant risk factor for breast cancer incidence and prognosis is breast density. How this links with biological cascade that underpins the ability of breast cancer cells metastasise and colonise the bone is unknown. We have developed alginate-based biomaterials, functionalised to mimic the stiffness of distinct stages of breast cancer progression, and bioactive hydrogels that mimic the bone microenvironment. Encapsulation of breast cancer/bone cell populations offers the possibility of generating physiologically relevant 3D tissue engineered models through the combination of materials and cells. Further, the inclusion of 3D models in a microfluidic system will mimic the blood vessels that cancer cells use as passage way for metastasis, hence enable the interconnection and modelling of the breast-to-bone dissemination.