| Popis: |
Metastatic breast cancer is one of the deadliest forms of malignancy, primarily driven by its characteristic microenvironment comprising of cancer cells interacting with stromal components. These interactions induce genetic and metabolic alterations creating a conducive environment for tumor growth. In this study, we developed a physiologically-relevant three dimensional (3D) vascularized breast cancer microenvironment comprising of metastatic MDA-MB-231 cells and human umbilical vein endothelial cells (HUVEC) loaded in human dermal fibroblasts (HDF) laden fibrin, representing the tumor stroma. The matrix as well as stromal cell density impacted the transcriptional profile of genes involved in tumor angiogenesis and cancer invasion, which are hallmarks of cancer. Cancer-specific canonical pathways and activated upstream regulators were also identified by the differential gene expression signatures of these composite cultures. Additionally, a tumor associated vascular bed of capillaries is established exhibiting dilated vessel diameters, representative of in vivo tumor physiology. Further, employing aspiration-assisted bioprinting, we identified cancer-endothelial crosstalk, in the form of collective angiogenesis of tumor spheroids bioprinted at close proximity. Overall, this bottom-up approach of tumor microenvironment fabrication provides an insight into the potential of in vitro tumor models and enables identification of novel therapeutic targets as a pre-clinical drug screening platform. |
