Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens

Shimamura, Takeshi; Saito, Satoru; Morita, Katsumi; Kitamura, Takehiko; Morimoto, Manabu; Kiba, Takayoshi; Numata, Kazushi; Tanaka, Katsuaki; Sekihara, Hisahiko

doi:10.1046/j.1440-1746.2000.02201.x

Cited by 44 publications

(29 citation statements)

References 31 publications

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“…VEGF mRNA expression was not significantly changed after a short pe- riod of ischemia during surgery (data not shown). Shimamura et al 19 have also reported, using liver biopsy specimens, that there was no difference in VEGF mRNA expression between HCC and nontumorous tissue. VEGF expression has been reported to be induced by inflammatory cytokines by infiltrating lymphocytes, 13 which are often observed in chronic hepatitis and cirrhosis.…”

Section: Discussionmentioning

confidence: 94%

“…[14][15][16][17][18] However, in HCC the importance of VEGF expression and its relationship to clinicopathological features of the tumor are still controversial. Shimamura et al 19 have shown that VEGF expression in HCC was not different from that in the corresponding nontumorous portion of the liver. Moreover, according to the reports of Yamaguchi et al 20 and El-Assal et al, 21 VEGF expression did not correlate with angiogenesis or any clinicopathological features of HCC, suggesting that angiogenesis of HCC may not be controlled by VEGF alone but may be mediated by other angiogenic factors.…”

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confidence: 96%

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Angiopoietins and Tie–2 Expression in Angiogenesis and Proliferation of Human Hepatocellular Carcinoma

et al. 2003

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Human hepatocellular carcinoma (HCC) is a hypervascular tumor but the mechanisms underlying the process of angiogenesis are not fully understood. Angiopoietins (Ang) have been recently identified as ligands for Tie-2 receptor and are thought to be important factors in vascular maturation and stability during angiogenesis. In this study, we investigated the expression of Ang-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in surgically resected specimens from 46 patients with HCC to determine their potential role in tumor angiogenesis and its progression. VEGF messenger RNA (mRNA) was significantly up-regulated in HCC compared to normal liver tissue from patients with hepatic metastases. No differences were found between HCC and adjacent liver tissue. Meanwhile, Ang-2 mRNA expression in HCC was significantly increased when compared to adjacent liver tissue. On the other hand, Ang-1 and Tie-2 mRNA expression in HCC was not different from that in adjacent liver tissue. Immunohistochemical staining also showed increased Ang-2 protein in HCC. Furthermore, a high Ang-2/1 mRNA ratio in HCC was closely associated with tumor portal vein invasion, tumor diameter, and the microvessel density level as assessed by CD34 immunostaining. With regard to prognosis, the survival time for patients in the high Ang-2/1 mRNA ratio group was significantly poorer when compared with the low Ang-2/1 mRNA ratio group. In conclusion, an increased expression of Ang-2/1 in the presence of VEGF may play a critical role in promoting tumor angiogenesis and progression in human HCC. (HEPATOLOGY 2003;37:1105-1113

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 96%

Angiopoietins and Tie–2 Expression in Angiogenesis and Proliferation of Human Hepatocellular Carcinoma

et al. 2003

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“…Overexpression of VEGF may be induced by the hypoxic tumor environment (mediated by hypoxia-inducible factor 2-a), activation of EGF receptor (EGFR) and cyclo-oxygenase-2 signaling (Avila et al, 2006;Bangoura et al, 2007). Increased expression of VEGF and VEGF receptors (VEGFRs; which include VEGFR-1, -2 and -3) has been observed in HCC cell lines and tissues, as well as in the serum of patients with HCC (Shimamura et al, 2000;Ng et al, 2001;Dhar et al, 2002;Poon et al, 2004a). The hepatitis B x antigen has also been associated with the upregulation of VEGFR-3 (Lian et al, 2007).…”

Section: Vegf Receptor Signalingmentioning

confidence: 99%

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

2010

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“…The inflammatory condition via NF-κB signaling pathway boosts VEGF expression that acts not only on the proliferation of endothelial cells in the vasculature but also on the proliferation of cancer cells expressing VEGF-A receptor through downstream Akt/mTOR signaling (221,222). Increased VEGF and VEGF receptors (VEGFRs; which include VEGFR-1, -2 and -3) expression has been observed in HCC cell lines and tissues, as well as in the serum of patients with HCC (223)(224)(225)(226). The hepatitis Bx antigen has also been associated with the up-regulation of VEGFR-3 (227).…”

Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

The tumor microenvironment in hepatocellular carcinoma (Review)

et al. 2012

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Abstract. The tumor microenvironment has been largely studied as a dynamic system orchestrated by inflammatory cells, including cancer cells, stroma as well as the extracellular matrix. It is useful to describe and predict the phenotypic characteristics of cancer. Furthermore, a better understanding of its interplay with the various aspects of the tumor cells may be utilized for the discovery of novel molecular targets. Liver cancer is considered a model of the relation occurring between the tumor microenvironment and tumor development. The chronic inflammatory status of the liver, sustained by the infection of hepatitis viruses, as well as the production of cytokines and growth factors within the parenchyma, lead to an intricate microenvironment. The identification of novel molecular therapeutic targets may improve the outcome of patients with liver cancer as it remains the third leading cause of cancer death worldwide. In the present study, the tumor microenvironment in hepatocellular carcinoma (HCC) was explored by a review of the literature. Studies on hepatitis virus infections and the consequent chronic inflammatory status were examined. In this context, immune-mediated and/or virusrelated molecular mechanisms have been hypothesized as being responsible for liver cancer development. The interlink among HCC microenvironment components, comprising cellular elements, cytokines, growth factors and several proteins is also described together with the role of matrix metalloproteinases in HCC development. Finally, the rationale for targeting tumorstromal interface is summarized in the context of new therapeutic opportunities.

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Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens

Abstract: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.

Cited by 44 publications

References 31 publications

Angiopoietins and Tie–2 Expression in Angiogenesis and Proliferation of Human Hepatocellular Carcinoma

Angiopoietins and Tie–2 Expression in Angiogenesis and Proliferation of Human Hepatocellular Carcinoma

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

The tumor microenvironment in hepatocellular carcinoma (Review)

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