VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

Zhang, Lei; Wang, Jia‐Ning; Tang, Jun‐Ming; Kong, Xiaoni; Yang, Jian-Ye; Zheng, Fei; Guo, Ling‐Yun; Huang, Yong-Zhang; Zhang, Li; Lin, Tian; Cao, Shufen; Tuo, Chang-Hai; Guo, Hongli; Chen, Shiyou

doi:10.1007/s11033-011-1304-2

Cited by 83 publications

(75 citation statements)

References 29 publications

(33 reference statements)

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“…28 BBC3 is a proapoptotic BH3-only protein that can sensitize HCC cells to sorafenib-induced apoptosis. 29 Some tumor-promoting genes such as MYC, 30 EGFR, 31 VEGFA, 32 and NOTCH1 33 are downregulated by PP2Ac silencing. These results offer a molecular insight into the regulation of the aggressiveness of HCC by PP2Ac.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma

Gong

Feng

Song

et al. 2015

Cancer Biology & Therapy

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Protein phosphatase 2A (PP2A) is a heterotrimeric protein phosphatase consisting of a 36-k D catalytic C subunit (PP2Ac). This study aimed to explore the prognostic and biological significance of PP2Ac in human hepatocellular carcinoma (HCC). High PP2Ac expression was significantly (P < 0.01) associated with serum hepatitis B surface antigen positivity, serum hepatitis B e antigen positivity, liver cirrhosis, moderate to poor differentiation grade, advanced disease stage, intrahepatic metastasis, and early recurrence in HCC. Multivariate analysis revealed PP2Ac as an independent prognostic factor for overall survival. Enforced expression of hepatitis B virus X protein (HBx) and its carboxyl-terminal truncated isoform induced PP2Ac expression in HCC cells. Co-immunoprecipitation assay revealed a direct interaction between PP2Ac and HBx. Small interfering RNA-mediated knockdown of PP2Ac significantly inhibited in vitro cell proliferation, colony formation, migration, and invasion and reduced tumor growth in an xenograft mouse model. In contrast, overexpression of PP2Ac promoted HCC cell proliferation, colony formation, and tumorigenesis. Additionally, silencing of PP2Ac impaired the growth-promoting effects on HepG2 HCC cells elicited by overexpression of carboxyl-terminal truncated HBx. Gene expression profiling analysis showed that PP2Ac downregulation modulated the expression of numerous genes involved in cell cycle and apoptosis regulation. Collectively, PP2Ac upregulation has a poor prognostic impact on the overall survival of HCC patients and contributes to the aggressiveness of HCC. PP2Ac may represent a potential therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma

Gong

Feng

Song

et al. 2015

Cancer Biology & Therapy

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“…Vascular endothelial growth factor (VEGF) is located at human chromosome 6p21.3 (Kong et al, 2007) and is produced by several cell types, including fibroblasts, smooth muscle cells, hypertrophic chondrocytes and osteoblasts (Ferrara et al, 2003). VEGF is an angiogenesis-promoting factor that plays an important role in the development of cancer and is necessary for primary tumor growth, invasion, and metastasis (Zhang et al, 2012). There are studies showing that single nucleotide polymorphisms (SNPs) in VEGF are a predictive factor of survival in patients with HCC resection (Kong et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Influence of vascular endothelial growth factor and alpha-fetoprotein on hepatocellular carcinoma

Yvamoto¹,

Fernandes-Ferreira²,

Nogueira³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We evaluated the influence of the vascular endothelial growth factor (VEGF) -C936T polymorphism on prognosis of hepatocellular carcinoma (HCC), cirrhosis, and hepatitis C virus (HCV) infection. Serum VEGF and alpha-fetoprotein (AFP) levels were determined and used to characterize sensitivity and specificity. A total of 285 subjects were studied: 68 HCC, 118 cirrhosis, 43 HCV, and 56 healthy controls. Prevalence of the VEGF -C936T polymorphism and serum levels of VEGF and AFP were analyzed by polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. The genotype CC (frequencies between 63.24 and 76.79%; P > 0.05) and the C allele (absolute frequencies from 0.816 to 0.884, P > 0.05) were prevalent in all groups. Higher VEGF levels in HCC patients (588.0 ± 501.0 pg/mL) 17454 E.Y. Yvamoto et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 17453-17462 (2015) were observed, particularly in patients with the T allele in VEGF -C936T (764.4 ± 571.7 pg/mL) compared to those in the other groups (P < 0.05). The same trend occurred with AFP levels (HCC = 8.522 ± 23.830; cirrhosis = 12.7 ± 59.3; HCV = 4.6 ± 4.7; control = 2.7 ± 1.8 ng/mL; P = 0.005). Levels of VEGF and AFP showed sensitivity of 65 and 28% and specificity of 85 and 99%, respectively, for HCC patients. In conclusion, the VEGF -C936T polymorphism is not associated with HCC but the mutant allele (T) increases VEGF levels in HCC patients. VEGF could be a potential biomarker for HCC, while AFP could be used to distinguish between patients with HCC and cirrhosis or HCV.

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“…Of note, VEGF receptor expression levels have also been found to correlate with the development of tumor. [8] Epidermal growth factor (EGF), another key regulator of cell survival and proliferation, is another biomarker identified in the pathogenesis and progression of different types of cancer. [9] During 1980s, several reports described the overexpression of EGF and EGF receptor (EGFR) in a variety of epithelial tumors, which may have a critical role in the etiology of human cancers.…”

Section: Introductionmentioning

confidence: 99%

Association of serum levels of epidermal growth factor with disease severity in patients with unresectable hepatocellular carcinoma

Kohla¹,

Al-Haddad²,

Nada³

et al. 2015

Hepatoma Res

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Aim: Epidermal growth factor (EGF) is a mitogen for hepatocyte grown in vitro, and its expression is up-regulated during liver regeneration. EGF also plays an important role in tumor initiation and progression. The goal of this study is to assess whether EGF is associated with advanced hepatocellular carcinoma (HCC) and also whether it is a predictive factor of shortened survival. Methods: Serum EGF levels were evaluated in a total of 151 subjects: 51 patients with unresectable HCC, (21 of them were eligible for transarterial chemoembolization (TACE) and serum EGF levels were measured before and 1 week after TACE), 40 patients with chronic hepatitis without cirrhosis, 40 patients with cirrhosis, and 20 healthy controls. Patient demographic and laboratory variables were evaluated as predictive factors of survival in a Cox regression multivariate analysis using SPSS software. Results: The mean serum level of EGF in patients with HCC was 784.49 pg/mL, which was significantly higher (P < 0.05) than all other groups. Mean EGF level in cirrhotic patients was 144.69 pg/mL; in those with chronic hepatitis C without cirrhosis, it was 338.64 pg/mL; and in healthy controls, it was 297.15 pg/mL. In group Ia patients who underwent TACE, the mean serum level of EGF was 759.76 ± 287.88 pg/mL before TACE, and 801.14 ± 276.12 pg/mL 1 week after treatment (P = 0.34). On multivariate Cox regression analysis only age (P = 0.03) and higher serum EGF level (P = 0.005), were inversely correlated with overall survival. Conclusion: EGF levels were found to be significantly higher in HCC patients and together with age were the only predictors of poor survival in these patients. There was an increase in EGF levels 1 week after TACE in response to hypoxia; however, this increase was not statistically significant.

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VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

Cited by 83 publications

References 29 publications

Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma

Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma

Influence of vascular endothelial growth factor and alpha-fetoprotein on hepatocellular carcinoma

Association of serum levels of epidermal growth factor with disease severity in patients with unresectable hepatocellular carcinoma

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