TY - JOUR
T1 - In vitro vascularized tumor platform for modeling tumor-vasculature interactions of inflammatory breast cancer
AU - Gadde, Manasa
AU - Phillips, Caleb
AU - Ghousifam, Neda
AU - Sorace, Anna G.
AU - Wong, Enoch
AU - Krishnamurthy, Savitri
AU - Syed, Anum
AU - Rahal, Omar
AU - Yankeelov, Thomas E.
AU - Woodward, Wendy A.
AU - Rylander, Marissa N.
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - HER2+ breast cancer
KW - angiogenesis
KW - collagen
KW - endothelium
KW - in vitro
KW - inflammatory breast cancer
KW - microfluidics
KW - sprouting
KW - triple negative breast cancer
KW - vasculature
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U2 - 10.1002/bit.27487
DO - 10.1002/bit.27487
M3 - Article
C2 - 32648934
AN - SCOPUS:85088273399
SN - 0006-3592
VL - 117
SP - 3572
EP - 3590
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
IS - 11
ER -