期刊
CANCER LETTERS
卷 404, 期 -, 页码 19-28出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.07.006
关键词
Fibroblasts; Intrahepatic metastasis; Cancer stem cells; IL-6; CCL2; CXCL8
类别
资金
- Funds for National Key Sci-Tech Special Project of China [2017YFA0504503, 2017ZX10203204-005-004]
- National Natural Science Foundation of China [81630070, 81372312, 81472737, 81372330, 81402018, 81572444, 81401308, 81402026, 81402454, 81502417, 81502543, 81402020]
- Science and Technology Commission of Shanghai Municipality, STCSM, China [15PJ1410600, 16JC1405200, 142D1900403, 16ZR1400200, 16YF1415000]
- Science Fund for Creative Research Groups, NSFC, China [81521091]
Fibroblasts have been reported to play an important role in hepatocellular carcinoma (HCC). However, the role of fibroblasts have not been fully understood. Conditioned medium collected from human pedtumor tissue-derived fibroblasts (CM-pTAFs) showed high metastasis ability than human HCC tissues derived fibroblasts (CM TAFs). To determine what component was secreted from fibroblasts, we used Bio-Plex analysis system and compared the factors secreted from CM-pTAFs and CM-TAFs, found a series of up-regulated cytokines in the CM-pTAFs, including IL-6, CCL2, CXCL1, CXCL8, SCGF-beta, HGF and VEGF. Pretreatment of IL-6 inhibitor Tocilizumab could inhibit metastasis the HCC cell treated with CM-pTAFs in vitro and in vivo. The expression of CCR2 and CXCR1 were up-regulated after CM-pTAFs treatment in HCC cell line SMMC-7721. Flow cytometric analysis experiment showed that most CCR2 or OCCR1 positive cells were also EpCAM positive. In vitro studies also showed that CM-pTAFs could increase sternness of SMMC-7721. In addition, neutralization of SCGF-beta and HGF could significantly reduce metastasis and viability of cancer stem cells treated with CM-pTAFs. Taken together, these results indicated that the peri-tumor tissues derived fibroblasts may promote development of HCC by recruiting cancer stem cells and maintaining their stemness characteristic. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据