A cancer invasion model of cancer-associated fibroblasts aggregates combined with TGF-β1 release system

Teruki Nii, Kimiko Makino, Yasuhiko Tabata

Research output: Contribution to journalArticle

Abstract

Introduction: The objective of this study is to design a cancer invasion model where the cancer invasion rate can be regulated in vitro. Methods: Cancer-associated fibroblasts (CAF) aggregates incorporating gelatin hydrogel microspheres (GM) containing various concentrations of transforming growth factor-β1 (TGF-β1) (CAF-GM-TGF-β1) were prepared. Alpha-smooth muscle actin (α-SMA) for the CAF aggregates was measured to investigate the CAF activation level by changing the concentration of TGF-β1. An invasion assay was performed to evaluate the cancer invasion rate by co-cultured of cancer cells with various CAF-GM-TGF-β1. Results: The expression level of α-SMA for CAF increased with an increased in the TGF-β1 concentration. When co-cultured with various types of CAF-GM-TGF-β1, the cancer invasion rate was well correlated with the α-SMA level. It is conceivable that the TGF-β1 concentration could modify the level of CAF activation, leading to the invasion rate of cancer cells. In addition, at the high concentrations of TGF-β1, the effect of a matrix metalloproteinase (MMP) inhibitor on the cancer invasion rate was observed. The higher invasion rate would be achieved through the higher MMP production. Conclusions: The present model is promising to realize the cancer invasion whose rate can be modified by changing the TGF-β1 concentration.

Original languageEnglish
Pages (from-to)196-204
Number of pages9
JournalRegenerative Therapy
Volume14
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Anti-cancer drug screening
  • Cancer invasion model
  • Drug delivery system
  • Gelatin hydrogel microspheres
  • Three-dimensional cell culture

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