Gastric-cancer-derived mesenchymal stem cells: a promising target for resveratrol in the suppression of gastric cancer metastasis
Gastric-cancer-derived mesenchymal stem cells: a promising target for resveratrol in the suppression of gastric cancer metastasis
复制标题
胃癌来源的间充质干细胞：白藜芦醇抑制胃癌转移的一个有前景的靶点
DOI：
10.1007/s13577-020-00339-5
复制
发表时间：
2020-04-29
期刊：
影响因子：
4.3
通讯作者：
Qian, Hui
中科院分区：
文献类型：
--
作者：
Yin, Lei;Zhang, Rongxue;Qian, Hui
肿瘤微环境（TM）是肿瘤进展的重要因素。间充质干细胞（MSC）是TM的重要组成部分，在癌症转移中发挥着关键作用。白藜芦醇（RES）是一种潜在的抗肿瘤药物，引起了广泛的关注。然而，目前尚不清楚RES是否可以通过靶向位于TM的MSC来发挥其抗肿瘤活性。在这项研究中，我们证明胃癌源性间充质干细胞（GC-MSCs）的条件培养基可促进胃癌（GC）转移并促进GC细胞上皮间质转化（EMT）的进展。然而，用RES预处理后，GC-MSCs对GC细胞的促转移作用被逆转。此外，RES减少GC-MSC（IL-6、IL-8、MCP-1、VEGF）基因表达和蛋白质分泌，并抵消GC-MSC诱导的GC细胞Wnt/β-catenin信号传导的激活，减少β-catenin核转运并降低GC细胞中β-catenin、CD44和CyclinD3的表达。 β-catenin 的重新表达削弱了 RES 对 GC 细胞的抑制作用。总之，RES 通过灭活 Wnt/β-catenin 信号传导来限制 GC 细胞的迁移性增加，并逆转 GC-MSC 诱导的 EMT 进程。 GC-MSCs 是 RES 抑制 GC 转移的有希望的靶标。
The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC-MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC-MSCs on GC cells was reversed. Furthermore, RES reduced GC-MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC-MSC-induced Wnt/beta-catenin signaling of GC cells, with less beta-catenin nuclear transport and declined expression of beta-catenin, CD44, and CyclinD3 in GC cells. Re-expression of beta-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC-MSCs by inactivating the Wnt/beta-catenin signaling. GC-MSCs are promising target for RES in the inhibition of GC metastasis.