OncoTargets and Therapy (Jul 2019)
TGFβ1 is essential for MSCs-CAFs differentiation and promotes HCT116 cells migration and invasion via JAK/STAT3 signaling
Abstract
Hao-Xiang Tan,1–3 Zhen-Bin Cao,4 Ting-Ting He,5 Tao Huang,1,3 Cai-Ling Xiang,1,3 Yu Liu1,31Department of Gastrointestinal Surgery, Hunan Provincial People’s Hospital, Changsha 410002, People’s Republic of China; 2Department of Gastrointestinal Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People’s Republic of China; 3Department of Gastrointestinal Surgery, First Affiliated Hospital of Hunan Normal University, Changsha 410002, People’s Republic of China; 4Department of Radiology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People’s Republic of China; 5Department of Pathology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People’s Republic of ChinaBackground 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.Keywords: TGFβ1, JAK/STAT3, MSCs-CAFs differentiation, migration and invasion