In Vitro Vascularized Tumor Platform for Modeling Tumor-Vasculature Interactions of Inflammatory Breast Cancer

TL;DR

This study developed a 3D in vitro vascularized breast tumor platform to investigate tumor-vasculature interactions specific to inflammatory breast cancer, revealing key differences in vessel permeability, VEGF expression, and endothelial sprouting compared to non-IBC models.

Contribution

The paper introduces the first 3D vascularized in vitro platform specifically modeling IBC tumor-vasculature interactions, enabling detailed study of tumor progression mechanisms.

Findings

IBC platforms showed higher vessel permeability and VEGF levels.

Unique endothelial sprouting observed in MDA-IBC3 platform.

Vessels encircled tumor clusters mimicking in vivo IBC features.

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, 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.