Macrophages-Triggered Sequential Remodeling of Endothelium-Interstitial Matrix to Form Pre-Metastatic Niche in Microfluidic Tumor Microenvironment

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2019 Jun 11

PMID 31179226

Citations 51

Authors

Hyunho Kim

Hyewon Chung

Jaehoon Kim

Dong-Hee Choi

Yoojin Shin

Yong Guk Kang

Beop-Min Kim

Sang-Uk Seo

Seok Chung

Seung Hyeok Seok

Affiliations

Soon will be listed here.

Abstract

The primed microenvironment of future metastatic sites, called the pre-metastatic niche, is a prerequisite for overt metastasis. However, a mechanistic understanding of the contributions of recruited cells to the niche is hindered by complex in vivo systems. Herein, a microfluidic platform that incorporates endothelial cells and extracellular matrix (ECM) scaffolds is developed, and the distinct role of recruited monocytes and macrophages in establishing pre-metastatic niches is delineated. It is observed that monocyte-derived matrix metalloproteinase 9 facilitates cancer cell extravasation through destruction of endothelial tight junctions. Furthermore, subsequent cancer cell invasiveness is significantly enhanced. Close examination of ECM structures reveals that cancer cells move within characteristic "microtracks" generated by macrophages, suggesting that macrophages could serve as a compensatory mechanism for the reduced migratory capacity of cancer cells. Thus, the first evidence of monocyte/macrophage-induced remodeling is shown, and these findings will open up new horizons for improving characterization of the pre-metastatic niche and corresponding immunotherapies.

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