Crosstalk Between Tumor Cells and Endothelial Cells In 3D Spheroids

Mimicking the tumor microenvironment is a major challenge in the effort of developing a model for cancer. In order to provide a model that can be reliably used for drug development and for personalized cancer therapy, it is critical to maintain key tissue features of the original. Spheroids are a 3-dimentional cellular model composed of self-assembled cell aggregates. Spheroids possess important components of cell-cells interactions as well as spatial growth. Using imprinted microwell array we optimized spheroid growth and investigated tumor microenvironment (TME) specific interconnection between tumor and endothelial cells (EC) in hybrid spheroids containing tumor cell (TC) lines or patient derived cancer cells. Spheroid morphology and tissue-like features were analyzed histologically. Our findings show that capillary-like structures are formed upon assembly and growth of TC:EC spheroids and that spheroids` shape and surface texture may be used as an indicator for the invasiveness of cells in the extra-cellular matrix. Creating such a model of hybrid tumor/endothelial spheroids has a crucial importance in the development of clinically-relevant model for personalized medicine and may offer the basis for a reliable and convenient method for predicting drug effects in patients.