In vitro vascularized tumor platform for modeling tumor‐vasculature interactions of inflammatory breast cancer.

Inflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor‐stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three‐dimensional, in vitro, vascularized, microfluidic IBC platform to quantify the spatial and temporal dynamics of tumor‐vasculature and tumor‐ECM interactions specific to IBC. Platforms consisting of collagen type 1 ECM with an endothelialized blood vessel were cultured with IBC cells, MDA‐IBC3 (HER2+) or SUM149 (triple negative), and for comparison to non‐IBC cells, MDA‐MB‐231 (triple negative). Acellular collagen platforms with endothelialized blood vessels served as controls. SUM149 and MDA‐MB‐231 platforms exhibited a significantly (p <.05) higher vessel permeability and decreased endothelial coverage of the vessel lumen compared to the control. Both IBC platforms, MDA‐IBC3 and SUM149, expressed higher levels of vascular endothelial growth factor (p <.05) and increased collagen ECM porosity compared to non‐IBCMDA‐MB‐231 (p <.05) and control (p <.01) platforms. Additionally, unique to the MDA‐IBC3 platform, we observed progressive sprouting of the endothelium over time resulting in viable vessels with lumen. The newly sprouted vessels encircled clusters of MDA‐IBC3 cells replicating a key feature of in vivo IBC. The IBC in vitro vascularized platforms introduced in this study model well‐described in vivo and clinical IBC phenotypes and provide an adaptable, high throughput tool for systematically and quantitatively investigating tumor‐stromal mechanisms and dynamics of tumor progression. [ABSTRACT FROM AUTHOR]