Nii Teruki, Makino Kimiko, Tabata Yasuhiko
Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, 278-8510, Japan.
Regen Ther. 2020 Mar 4;14:196-204. doi: 10.1016/j.reth.2020.02.003. eCollection 2020 Jun.
The objective of this study is to design a cancer invasion model where the cancer invasion rate can be regulated .
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 whose rate can be modified by changing the TGF-β1 concentration.
本研究的目的是设计一种癌症侵袭模型,在该模型中癌症侵袭率能够得到调控。
制备包含含有不同浓度转化生长因子-β1(TGF-β1)的明胶水凝胶微球(GM)的癌症相关成纤维细胞(CAF)聚集体(CAF-GM-TGF-β1)。通过改变TGF-β1的浓度来测量CAF聚集体中的α平滑肌肌动蛋白(α-SMA),以研究CAF的激活水平。通过将癌细胞与各种CAF-GM-TGF-β1共培养来进行侵袭试验,以评估癌症侵袭率。
CAF的α-SMA表达水平随TGF-β1浓度的增加而升高。当与各种类型的CAF-GM-TGF-β1共培养时,癌症侵袭率与α-SMA水平密切相关。可以想象,TGF-β1浓度可以改变CAF的激活水平,从而导致癌细胞的侵袭率。此外,在高浓度TGF-β1时,观察到基质金属蛋白酶(MMP)抑制剂对癌症侵袭率的影响。通过更高的MMP产生可实现更高的侵袭率。
本模型有望实现通过改变TGF-β1浓度来调节侵袭率的癌症侵袭。