Engineered cancer in vitro model to demultiplex biophysical cues in metastasis

乳腺癌是英国女性最常见的癌症。虽然低级别乳腺癌患者的预后不断改善，但70%的晚期乳腺癌患者发生无法治愈的骨转移。驱动靶向转移的机制是复杂的，需要改变原发肿瘤和转移小生境。乳腺癌发病率和预后的一个重要危险因素是乳腺密度。这与支撑乳腺癌细胞转移和定居骨骼能力的生物级联反应如何联系尚不清楚。我们已经开发了基于藻酸盐的生物材料，功能化以模拟乳腺癌进展的不同阶段的硬度，以及模拟骨微环境的生物活性水凝胶。乳腺癌/骨细胞群的包封提供了通过材料和细胞的组合产生生理相关的3D组织工程模型的可能性。此外，在微流体系统中包含3D模型将模拟癌细胞用作转移通道的血管，从而实现乳房到骨骼传播的互连和建模。

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.