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

Regenerative Therapy
Teruki NiiYasuhiko Tabata

Abstract

The objective of this study is to design a cancer invasion model where the cancer invasion rate can be regulated in vitro. 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. 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. The present model is promising to realize the cancer invasion ...Continue Reading

Citations

Oct 7, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fakhrossadat EmamiSimmyung Yook
Aug 28, 2021·International Journal of Molecular Sciences·Teruki Nii, Yoshiki Katayama

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