Back to Search
Start Over
In vitro vascularized tumor platform for modeling tumorāvasculature interactions of inflammatory breast cancer
- Source :
- Biotechnol Bioeng
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
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, 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.
- Subjects :
- Endothelium
Angiogenesis
Bioengineering
Applied Microbiology and Biotechnology
Article
Metastasis
Extracellular matrix
chemistry.chemical_compound
In vivo
Cell Line, Tumor
Cell Behavior (q-bio.CB)
medicine
Humans
Cell Culture Techniques, Three Dimensional
Tissues and Organs (q-bio.TO)
skin and connective tissue diseases
Neovascularization, Pathologic
Chemistry
Quantitative Biology - Tissues and Organs
medicine.disease
Extracellular Matrix
Vascular endothelial growth factor
Intercellular Junctions
medicine.anatomical_structure
Tumor progression
FOS: Biological sciences
Cancer research
Quantitative Biology - Cell Behavior
Cytokines
Female
Inflammatory Breast Neoplasms
Collagen
Endothelium, Vascular
Biotechnology
Blood vessel
Subjects
Details
- ISSN :
- 10970290 and 00063592
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Biotechnology and Bioengineering
- Accession number :
- edsair.doi.dedup.....2657940f5064b6c021ef193818c816ad