PMID- 27044356 OWN - NLM STAT- MEDLINE DCOM- 20161226 LR - 20181113 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 33 IP - 5 DP - 2016 May TI - FGFR3 promotes angiogenesis-dependent metastasis of hepatocellular carcinoma via facilitating MCP-1-mediated vascular formation. PG - 46 LID - 10.1007/s12032-016-0761-9 [doi] AB - The biological role of fibroblast growth factor receptor 3 (FGFR3) in tumor angiogenesis of hepatocellular carcinoma (HCC) has not been discussed before. Our previous work had indicated FGFR3 was overexpressed in HCC, and silencing FGFR3 in Hu7 cells could regulate tumorigenesis via down-regulating the phosphorylation level of key members of classic signaling pathways including ERK and AKT. In the present work, we explored the role of FGFR3 in angiogenesis-dependent metastasis by using SMMC-7721 and QGY-7703 stable cell lines. Our results indicated FGFR3 could regulate in vitro cell migration ability and in vivo lung metastasis ability of HCC, which was in accordance with increased angiogenesis ability in vitro and in vivo. Using the supernatant from SMMC-7721/FGFR3 cells, we conducted a human angiogenesis protein microarray including 43 angiogenesis factors and found that FGFR3 modulated angiogenesis and metastasis of HCC mainly by promoting the protein level of monocyte chemotactic protein 1 (MCP-1). Silencing FGFR3 by short hairpin RNA (shRNA) could reduce MCP-1 level in lysates and supernatant of QGY-7703 cells and SMMC-7721 cells. Silencing MCP-1 in QGY-7703 or SMMC-7721 cells could induce similar phenotypes compared with silencing FGFR3. Our results suggested FGFR3 promoted metastasis potential of HCC, at least partially if not all, via facilitating MCP-1-mediated angiogenesis, in addition to previously found cell growth and metastasis. MCP-1, a key medium between HCC cells and HUVECs, might be a novel anti-vascular target in HCC. FAU - Liu, Xinyu AU - Liu X AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. FAU - Jing, Xiaoqian AU - Jing X AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. FAU - Cheng, Xi AU - Cheng X AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. FAU - Ma, Ding AU - Ma D AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. FAU - Jin, Zhijian AU - Jin Z AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. FAU - Yang, Weiping AU - Yang W AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. drqwh2003@yahoo.com. FAU - Qiu, Weihua AU - Qiu W AD - Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, China. drqwh2003@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160404 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - EC 2.7.10.1 (FGFR3 protein, human) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3) SB - IM MH - Animals MH - Carcinoma, Hepatocellular/blood supply/*pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Chemokine CCL2/genetics/*metabolism MH - Gene Expression Regulation, Neoplastic MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Liver Neoplasms/blood supply/*pathology MH - Male MH - Mice, Nude MH - Neovascularization, Pathologic/*genetics MH - Receptor, Fibroblast Growth Factor, Type 3/*genetics/metabolism MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - Angiogenesis OT - FGFR3 OT - Hepatocellular carcinoma OT - MCP-1 EDAT- 2016/04/06 06:00 MHDA- 2016/12/27 06:00 CRDT- 2016/04/06 06:00 PHST- 2015/12/13 00:00 [received] PHST- 2016/03/30 00:00 [accepted] PHST- 2016/04/06 06:00 [entrez] PHST- 2016/04/06 06:00 [pubmed] PHST- 2016/12/27 06:00 [medline] AID - 10.1007/s12032-016-0761-9 [pii] AID - 10.1007/s12032-016-0761-9 [doi] PST - ppublish SO - Med Oncol. 2016 May;33(5):46. doi: 10.1007/s12032-016-0761-9. Epub 2016 Apr 4.