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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615717 | PMC |
| http://dx.doi.org/10.2147/OTT.S178618 | DOI Listing |
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