Speaker
Description
Invasion of cancer cells into surrounding tissue represents the first step of metastasis and is strongly controlled by the tumor microenvironment. In breast cancer, adipose‐derived stromal cells (ASCs) from adjacent adipose tissue are increasingly recognized as important regulators of this process, but the underlying mechanisms remain unclear. While bioprinting offers unique advantages for investigating tumor-stroma interactions, its potential has been limited by a lack of bioinks that support cell migration. To address this, we developed a migration-permissive bioink and generated a fully 3D bioprinted breast cancer-stroma model to analyze the migration and invasion dynamics of tumor cells in response to neighboring ASCs.
Various methacrylated collagen type I (ColMA)-based bioinks were characterized regarding printability, rheology, mechanics, and ultrastructure. Cell viability and migration capacity of MDA-MB-231 breast cancer cells in ColMA bioinks were analyzed by live/dead staining and spheroid invasion assays. Utilizing extrusion-based bioprinting, we generated compartmentalized co-culture constructs. Printed constructs were imaged over 4 days, capturing brightfield and fluorescence z-stacks. After image deconvolution and segmentation, cancer cell migration in x/y/z-direction was tracked for computing key migration parameters including track length, speed, sphericity, displacement towards and invasion into the stromal compartment.
After bioprinting, constructs displayed a fibrous collagen network morphology and high cell viability (>90 %). Migration of MDA-MB-231 cells was shown to be highly dependent on matrix remodeling via matrix metalloproteases and influenced significantly by ASCs. 3D real-time tracking of migrating tumor cells within the bioprinted co-culture model revealed that ASCs within the stromal compartment markedly enhanced migration and invasion parameters, as evidenced by an increase in mean track speeds by 29 %, a distinct displacement towards stroma, and a 2.5-fold increase in the number of invading cells. Further, a linear correlation between cell speed and cell sphericity suggests that ASC-driven morphological changes boost migration speed. This 3D bioprinted model reveals new insights how stromal cells from adipose tissue influence the invasion dynamics of breast cancer, and thus holds strong potential for anti-metastatic drug screening.
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