Tumor stromal interactions have been shown to be the driving force behind the poor prognosis associated with aggressive breast tumors. These interactions, specifically between tumor and the surrounding ECM, and tumor and vascular endothelium, promote tumor formation, angiogenesis, and metastasis . In this study, we develop an in vitrovascularized tumor platform that allows for investigation of tumor-stromal interactions in three breast tumor derived cell lines of varying aggressiveness: MDA-IBC3, SUM149, and  MDA-MB-231 . The platform recreates key features of breast tumors, including increased vascular permeability, vessel sprouting, and ECM remodeling. Morphological and quantitative analysis reveals differential effects from each tumor cell type on endothelial coverage, permeability, expression of VEGF, and collagen remodeling. Triple negative tumors, SUM149 and MDA-MB-321, resulted in a significantly (p<0.05) higher endothelial permeability and decreased endothelial coverage  compared to the control TIME only platform. SUM149 /TIME platformswere 1.3 fold lower (p<0.05) , and MDA-MB-231 /TIME platforms were 1.5 fold lower (p< 0.01) in endothelial coverage compared to the control TIME only platform. HER2+ MDA-IBC3 tumor cells expressed high levels of VEGF (p<0.01) and induced vessel sprouting. Vessels sprouting was tracked for 3 weeks and with increasing time exhibited formation of multiple vessel sprouts that invaded into the ECM and surrounded clusters of MDA-IBC3 cells . Both IBC cell lines, SUM149 and MDA-IBC3, resulted in a collagen ECM with significantly greater porosity with 1.6 and 1.1 fold higher compared to control, p<0.01. The breast cancer in vitro vascularized platforms introduced in this paper are an adaptable, high throughout tool for unearthing tumor-stromal mechanisms and dynamics behind tumor progressionand may prove essential in developing effective targeted therapeutics .
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, breast tumor 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). An acellular collagen platform with an endothelial blood vessel served as control. SUM149 and MDA-MB-231 platforms exhibited a significantly (p<0.05) 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 VEGF (p<0.05) and increased collagen ECM porosity compared to non-IBC MDA-MB-231 (p< 0.05) and control (p<0.01) 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 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 throughout tool for systematically and quantitatively investigating tumor-stromal mechanisms and dynamics of tumor progression .
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Tumor stromal interactions have been shown to be the driving force behind the poor prognosis associated with aggressive breast tumors. These interactions, specifically between tumor and the surrounding ECM, and tumor and vascular endothelium, promote tumor formation, angiogenesis, and metastasis
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
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develop an in vitrovascularized tumor platform that allows for investigation of tumor-stromal interactions in three breast tumor derived cell lines of varying aggressiveness: MDA-IBC3, SUM149,
developed the first three-dimensional, in vitro, vascularized, breast tumor platform to quantify the spatial and temporal dynamics of tumor-vasculature
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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,
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. The platform recreates key features of breast tumors, including increased vascular permeability, vessel sprouting, and ECM remodeling. Morphological and quantitative analysis reveals differential effects from each tumor cell type on endothelial coverage, permeability, expression of VEGF, and collagen remodeling. Triple negative tumors,
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