3D Bioprinted Breast Cancer‐Stroma Model with Tailored Migration‐Permissive Bioink Reveals Impact of Adipose‐Derived Stromal Cells on Cancer Cell Migration and Invasion Dynamics

ABSTRACT In breast cancer, local invasion of cancer cells into surrounding tissue marks the first step of metastasis. However, to elucidate the impact of cells from the tumor microenvironment on this process, advanced 3D migration models are still urgently needed. To enable migration and invasion studies in a fully 3D bioprinted tumor‐stroma model, a migration‐permissive bioink composed of methacrylated collagen type I and thiolated hyaluronic acid with low polymer content is developed. In a printed co‐culture model comprising metastatic breast cancer cells (MDA‐MB‐231) and adipose‐derived stromal cells (ASCs), real‐time single‐cell tracking reveals that ASCs in the stromal compartment profoundly promote migration and invasion dynamics of individual tumor cells. This is reflected by increased speed, migration distance, and invasion into the stroma, and is accompanied by collagen remodeling and a shift in tumor cell morphology. A correlation between tumor cell morphology and migration speed is evident, which is modulated by ASCs. A highly motile and invasive subset of tumor cells is significantly enhanced in the presence of ASCs. These insights into the influence of ASCs on the heterogeneity of breast cancer cells in terms of their migratory behavior may inform the development of more specific and effective treatment options for metastatic breast cancer.