Conclusion
The 3D in vitro vascularized IBC platforms presented in this work
enabled us to dynamically characterize and model the IBC tumor-vascular
interactions, as well as determine the spatiotemporal response of these
interactions on vascular permeability and matrix porosity not possible
with existing in vitro or in vivo models. The platforms
provide a robust and cost-effective means to systematically and
quantitatively investigate IBC in a controlled and replicable manner
compared to the current standard of using PDX models. Using the in
vitro platform, we determined IBC cells were more active in remodeling
of the collagen ECM as well as secretion of proangiogenic and
tumorigenic factor VEGF compared to non-IBC MDA-MB-231, revealing
potential targets for IBC therapeutics. For the first time, we induced
angiogenic sprouting of the vascular endothelium and vascular
surrounding of tumor emboli (unique behaviors of IBC tumors) purely
through tumor-endothelial cell interactions and characterized sprouting
in a spatial and temporal fashion in an in vitro setting.
Furthermore, our system captures blood vessel leakiness and increased
matrix porosity, representative behavior of in vivo invasive
tumors. With the in vitro vascularized IBC tumor platforms,
behavioral variations that are representative of in vivo tumors
can be identified and distinguished as a result of the different breast
cancer cells. This platform allows for spatiotemporal imaging and
identification of biological proteins and responses which may play a
direct role in tumorigenesis and vascularization in vivo and
represent a useful tool for studying various aggressive breast cancers
whose phenotype is driven by tumor-stromal-vascular interactions. These
platforms can be further expanded to investigate increasingly complex
cell type interactions, thereby providing a tool to further decipher the
mechanisms behind development of these tumors.