Studying Tumor Angiogenesis and Cancer Invasion in a Three-Dimensional Vascularized Breast Cancer Micro-Environment.

Document Type

Article

Publication Date

4-15-2021

Publication Title

Adv Biol (Weinh)

Keywords

JGM

JAX Source

Adv Biol (Weinh) 2021 Apr 15; e2100090

First Page

2100090

Last Page

2100090

ISSN

2701-0198

PMID

33857356

DOI

https://doi.org/10.1002/adbi.202100090

Grant

CA224422

Abstract

Metastatic breast cancer is one of the deadliest forms of malignancy, primarily driven by its characteristic micro-environment comprising cancer cells interacting with stromal components. These interactions induce genetic and metabolic alterations creating a conducive environment for tumor growth. In this study, a physiologically relevant 3D vascularized breast cancer micro-environment is developed comprising of metastatic MDA-MB-231 cells and human umbilical vein endothelial cells loaded in human dermal fibroblasts laden fibrin, representing the tumor stroma. The matrix, as well as stromal cell density, impacts the transcriptional profile of genes involved in tumor angiogenesis and cancer invasion, which are hallmarks of cancer. Cancer-specific canonical pathways and activated upstream regulators are also identified by the differential gene expression signatures of these composite cultures. Additionally, a tumor-associated vascular bed of capillaries is established exhibiting dilated vessel diameters, representative of in vivo tumor physiology. Further, employing aspiration-assisted bioprinting, cancer-endothelial crosstalk, in the form of collective angiogenesis of tumor spheroids bioprinted at close proximity, is identified. Overall, this bottom-up approach of tumor micro-environment fabrication provides an insight into the potential of in vitro tumor models and enables the identification of novel therapeutic targets as a preclinical drug screening platform.

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