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In Vitro Vascularized Tumor Platform for Modeling Tumor-Vasculature Interactions of Inflammatory Breast Cancer
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  • Manasa Gadde,
  • Caleb Phillips,
  • Neda Ghousifam,
  • Anna Sorace,
  • Enoch Wong,
  • Savitri Krishnamurthy,
  • Anum Syed,
  • Omar Rahal,
  • Thomas Yankeelov,
  • Wendy Woodward,
  • Marissa Rylander
Manasa Gadde
University of Texas at Austin
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Caleb Phillips
University of Texas at Austin
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Neda Ghousifam
University of Texas at Austin
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Anna Sorace
The University of Alabama at Birmingham School of Medicine
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Enoch Wong
University of Texas at Austin
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Savitri Krishnamurthy
University of Texas MD Anderson Cancer Center
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Anum Syed
University of Texas at Austin
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Omar Rahal
University of Texas MD Anderson Cancer Center
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Thomas Yankeelov
University of Texas at Austin
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Wendy Woodward
University of Texas MD Anderson Cancer Center
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Marissa Rylander
University of Texas at Austin
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Peer review status:ACCEPTED

25 Mar 2020Submitted to Biotechnology and Bioengineering
27 Mar 2020Submission Checks Completed
27 Mar 2020Assigned to Editor
19 Apr 2020Reviewer(s) Assigned
20 May 2020Editorial Decision: Revise Major
20 May 2020Review(s) Completed, Editorial Evaluation Pending
24 Jun 20201st Revision Received
24 Jun 2020Submission Checks Completed
24 Jun 2020Assigned to Editor
05 Jul 2020Reviewer(s) Assigned
08 Jul 2020Review(s) Completed, Editorial Evaluation Pending
08 Jul 2020Editorial Decision: Accept

Abstract

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, 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). 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.