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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number1900195
JournalAdvanced Science
DOIs
Publication statusPublished - 2019 Jan 1

Keywords

  • 3D microfluidic tumor microenvironment
  • macrophages
  • metastasis
  • monocytes
  • pre-metastatic niches

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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