转化生长因子β1（TGFβ1）对间充质干细胞向癌相关成纤维细胞（MSCs-CAFs）的分化至关重要，并通过JAK/STAT3信号通路促进HCT116细胞的迁移和侵袭。

TGFβ1 is essential for MSCs-CAFs differentiation and promotes HCT116 cells migration and invasion via JAK/STAT3 signaling.

作者信息

Tan Hao-Xiang, Cao Zhen-Bin, He Ting-Ting, Huang Tao, Xiang Cai-Ling, Liu Yu

机构信息

Department of Gastrointestinal Surgery, Hunan Provincial People's Hospital, Changsha 410002, People's Republic of China.

Department of Gastrointestinal Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People's Republic of China.

出版信息

Onco Targets Ther. 2019 Jul 5;12:5323-5334. doi: 10.2147/OTT.S178618. eCollection 2019.

BACKGROUND AND PURPOSE

Colorectal cancer (CRC) frequently metastasizes to the liver, which involves the participation of multiple cytokines. Tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs) and tumor cells acts as an essential factor in cancer metastasis. Transforming growth factor β1 (TGFβ1) is a vital cytokine involved in migration and invasion of cancer cells. However, the underlying mechanisms remain unclear. In the present study, we aimed to investigate the role and molecular mechanisms of TGFβ1 in TME.

METHODS

The conditioned medium prepared from colorectal cancer HCT116 and HT29 cells was used to culture mesenchymal stem cells (MSCs). The differentiation of MSCs to CAFs was detected by flow cytometry. The role of TGFβ1 in colorectal cancer cells metastasis was examined by wound-healing assay and transwell assay. And the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was measured by Western blot assay.

RESULTS

TGFβ1 induced the differentiation of MSCs to CAFs and improved HCT116 and HT29 cells migration and invasion. Meanwhile, TGFβ1 also upregulated the phosphorylation of STAT3 and enhanced the nuclear localization of p-STAT3, which activated JAK/STAT3 signaling pathway.

CONCLUSION

TGFβ1 induced the differentiation of MSCs into CAFs and promoted the migration and invasion of HCT116 and HT29 cells, which depended on the activation of JAK/STAT3 signaling pathway.

背景与目的

结直肠癌（CRC）常转移至肝脏，这涉及多种细胞因子的参与。由癌症相关成纤维细胞（CAFs）和肿瘤细胞组成的肿瘤微环境（TME）是癌症转移的重要因素。转化生长因子β1（TGFβ1）是一种参与癌细胞迁移和侵袭的重要细胞因子。然而，其潜在机制仍不清楚。在本研究中，我们旨在探讨TGFβ1在TME中的作用及分子机制。

方法

用结直肠癌HCT116和HT29细胞制备的条件培养基培养间充质干细胞（MSCs）。通过流式细胞术检测MSCs向CAFs的分化。通过伤口愈合试验和Transwell试验检测TGFβ1在结直肠癌细胞转移中的作用。通过蛋白质印迹法检测Janus激酶/信号转导子和转录激活子3（JAK/STAT3）信号通路的激活情况。