TEL: +86 571 56623320    EMAIL: [email protected]

Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metast
SUNLONG BIOTECH / 2024-01-09
  • Author:Ye, L. Y., Chen, W., Bai, X. L., Xu, X. Y., Zhang, Q., Xia, X. F., Sun, X., Li, G. G., Hu, Q. D., Fu, Q. H. & Liang, T. B.

  • Periodical:Cancer research 76, 818-830 (2016)

  • Article source

Portal vein tumor thrombosis (PVTT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and is therefore associated with poor prognosis. The presence of PVTT frequently accompanies substantial hypoxia within the tumor microenvironment, which is suggested to accelerate tumor metastasis, but it is unclear how this occurs. Recent evidence has shown that the hypoxia-inducible factor HIF-1α induces epithelial-to-mesenchymal transition (EMT) in tumor cells to facilitate metastasis. In this study, we investigated whether hypoxia-induced EMT in cancer cells also affects immune cells in the tumor microenvironment to promote immunosuppression. We found that hypoxia-induced EMT increased the expression of the CCL20 cytokine in hepatoma cells. Furthermore, coculture of monocyte-derived macrophages with hypoxic hepatoma cells revealed that the expression of indoleamine 2, 3-dioxygenase (IDO) was induced in monocyte-derived macrophages in a CCL20-dependent manner. In turn, these IDO-expressing monocyte-derived macrophages suppressed T-cell proliferation and promoted the expansion of immunosuppressive regulatory T cells. Moreover, high CCL20 expression in HCC specimens was associated with PVTT and poor patient survival. Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.

User Comment(Total0User Comment Num)

  • No comment
Total 0 records, divided into1 pages First Prev Next Last
Username: Anonymous user
E-mail:
Rank:
Content:
Verification code: captcha

Call us

+86 571 56623320

Address

Room 1-315, Kongle Changqing Building, No. 160 Guangye Road,Gongshu District, Hangzhou City, Zhejiang Province, China

Join Us with

Leave a message
* To protect against spam, please pass the CAPTCHA test below.