title: FGFR3 promotes angiogenesis-dependent metastasis of hepatocellular carcinoma via facilitating MCP-1-mediated vascular formation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Jing
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Weiping
authors.initials: W
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Weihua
authors.initials: W
authors.lastname: Qiu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Angiogenesis; FGFR3; Hepatocellular carcinoma; MCP-1