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- Title
The Role Of Hepatic Stellate Cells In Promoting Liver Metastasis Of Colorectal Carcinoma.
- Authors
Huang, Wen-Hai; Zhou, Min-Wei; Zhu, Yan-Feng; Xiang, Jian-Bin; Li, Zhen-Yang; Wang, Zi-Hao; Zhou, Yi-Ming; Yang, Yi; Chen, Zong-You; Gu, Xiao-Dong
- Abstract
Purpose: Colorectal cancer (CRC) is the most common malignancy in the gastrointestinal tract. The liver is the most common location of CRC metastases, which are the main causes of CRC-related death. However, the mechanisms underlying metastasis of CRC to the liver have not been characterized, resulting in therapeutic challenges. Methods: The effects of hepatic stellate cells (HSCs) on T cells were evaluated using in vitro mixed lymphocyte reactions (MLRs) and cytokine production assays. HSC-induced CT26 cell migration and proliferation were evaluated in vitro and in vivo. Results: HSCs induced T cell hypo-responsiveness, promoted T cell apoptosis, and induced regulatory T cell expansion in vitro. IL-2 and IL-4 were significantly lower in MLRs incubated with HSCs. Supernatants of MLRs with HSCs promoted CT26 cell proliferation and migration. Furthermore, the presence of HSCs increased the number of liver metastases and promoted proliferation of liver metastatic tumor cells in vivo. Conclusion: HSCs may contribute to an immunosuppressive liver microenvironment, resulting in a favorable environment for the colonization of CRC cells in the liver. These findings highlight a potential strategy for treatment of CRC liver metastases.
- Subjects
KUPFFER cells; LIVER cells; LIVER metastasis; SUPPRESSOR cells; CELL migration
- Publication
OncoTargets & Therapy, 2019, Vol 12, p7573
- ISSN
1178-6930
- Publication type
Article
- DOI
10.2147/OTT.S214409