Journal
CANCER LETTERS
Volume 404, Issue -, Pages 19-28Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.07.006
Keywords
Fibroblasts; Intrahepatic metastasis; Cancer stem cells; IL-6; CCL2; CXCL8
Categories
Funding
- 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]
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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.
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