癌症研究
CCL5
转移
CCL7型
CXCL16型
肿瘤微环境
趋化因子
生物
癌症
医学
CXCL10型
免疫学
内科学
炎症
T细胞
肿瘤细胞
白细胞介素2受体
免疫系统
作者
Jiao Liu,Sheng Chen,Wei Wang,Beifang Ning,Fei Chen,Weifeng Shi,Jin Ding,Wansheng Chen,Wei‐Fen Xie,Xin Zhang
出处
期刊:Cancer Letters
[Elsevier]
日期:2016-08-01
卷期号:379 (1): 49-59
被引量:170
标识
DOI:10.1016/j.canlet.2016.05.022
摘要
Fibroblasts are rich in the surrounding microenvironment of hepatocellular carcinoma (HCC) because most HCCs occur in fibrotic or cirrhotic livers. However, the role of cancer-associated fibroblasts (CAFs) in HCC metastasis remains obscure. Here, we reported that CAFs promote the migration and invasion of HCC cells in vitro and facilitate the HCC metastasis to the bone, brain and lung in NOD/SCID mice. The RayBio human chemokine antibody array revealed that CAFs secret higher levels of CCL2, CCL5, CCL7 and CXCL16 than peri-tumor fibroblasts. CCL2 and CCL5 increase the migration but not the invasion of HCC cells, while CCL7 and CXCL16 promote both migration and invasion of HCC cells. Moreover, CCL2 and CCL5 stimulate the activation of the hedgehog (Hh) pathway, while CCL7 and CXCL16 enhance the activity of the transforming growth factor-β (TGF-β) pathway in HCC cells. The neutralizing antibodies of chemokines notably attenuate the effect of CAFs on HCC metastasis and compromised the activation of Hh and TGF-β pathways in HCC cells. In summary, CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells.
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