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.

Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior

“…HCC is one of the most common cancers in the world, accounting for nearly half a million deaths worldwide 1 – 3 . Despite recent progress in diagnostic and therapeutic management, hepatocellular carcinoma (HCC) patient prognosis remains poor 4 . Radical surgical resection of the tumor is considered the only effective treatment for liver cancer, and provides a 5-year survival rate of 31% 5 .…”

The Effect of Botulinum Toxin Type A on Expression Profiling of Long Noncoding RNAs in Human Dermal Fibroblasts

“…Bioinformatic analysis reveals that FGFR3P which is located on chromosome 6 is defined as the pseudogene of Fibroblast Growth Factor Receptor 3 (FGFR3), noncoding RNA. FGFR3 is one member of FGFR family and had been reported to participate in the regulation of cell proliferation, apoptosis, migration, and angiogenesis in many cells including HDFs [ 36 – 39 ]. Although pseudogenes have been considered as the remnants of functional genes which have no coding ability over a long period of time, evergrowing number of studies have proved that some pseudogenes have diverse functions, including serving as miRNA decoys, functioning as antisense transcripts, encoding short peptides, and producing siRNAs or proteins [ 40 – 43 ].…”

Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma

“…In recent years, more and more researches employed Human Tumor Metastasis Microarray to dissect the gene function and form gene regulatory network in various of cancers [ 28 – 30 ]. Thus, the Human Tumor Metastasis Microarray is useful in searching for new therapeutic targeted genes and helpful in dissect mechanism of the gene in several of cancers [ 31 , 32 ]. The OHS-028 OligoGEArray Human Tumor Metastasis Microarray (Super Array, Bethesda, MD) was used to characterize the metastasis-related gene expression profiles of HCC tissues in this study.…”