Modelling bone metastasis in spheroids to study cancer progression and screen cisplatin efficacy

Abstract

Most bone metastases are caused by primary breast or prostate cancer cells settling in the bone microenvironment, affecting normal bone physiology and function and reducing 5-year survival rates to 10% and 6%, respectively. To expedite clinical availability of novel and effective bone metastases treatments, reliable and predictive in vitro models are urgently required to screen for novel therapies as current in vitro 2D planar mono-culture models do not accurately predict the clinical efficacy. We herein engineered a novel human in vitro 3D co-culture model based on spheroids to study dynamic cellular quantities of (breast or prostate) cancer cells and human bone marrow stromal cells and screen chemotherapeutic efficacy and specificity of the common anticancer drug cisplatin. Bone metastatic spheroids (BMSs) were formed rapidly within 24 h, while the morphology of breast versus prostate cancer BMS differed in terms of size and circularity upon prolonged culture periods. Prestaining cell types prior to BMS formation enabled confocal imaging and quantitative image analysis of in-spheroid cellular dynamics for up to 7 days of BMS culture. We found that cancer cells in BMS proliferated faster and were less susceptible to cisplatin treatment compared to 2D control cultures. Based on these findings and the versatility of our methodology, BMS represent a feasible 3D in vitro model for screening of new bone cancer metastases therapies.