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Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

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Abstract

Hepatocellular carcinoma (HCC) is naturally resistant to radiotherapy and cytotoxic chemotherapy, leaving surgery as the mainstream therapeutic approach. However, the 5-year recurrence rate after curative resection is as high as 61.5%. The background hepatitis B- or C-induced cirrhosis and the presence of micrometastases at the time of surgery have been regarded as two main causes of recurrence. Recently, accumulating evidence suggests that growth factors and cytokines released during the physiological process of post-surgical liver regeneration could induce the activation of dormant micrometastatic lesions. The establishment of neovasculature to support either liver regeneration or HCC growth involves multiple cell types including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and circulating endothelial progenitors. The crosstalks among these cells are driven by multiple molecules and signaling pathways, including vascular endothelial growth factors and their receptors, platelet-derived growth factor, the angiopoietin/Tie family, hepatocyte growth factor/c-Met signaling, and others. Anti-angiogenic agent targeting liver cancer vasculature has been reported to be able to generate limited survival benefit of the patients. In this review, discussions are focused on various angiogenic mechanisms of HCC and liver regeneration, as well as the prevailing anti-angiogenic strategies.

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Abbreviations

AAH:

Atypical adenomatous hyperplasia

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EPC:

Endothelial progenitor cell

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HGF:

Hepatocyte growth factor

HIF:

Hypoxia-inducible factor

HSC:

Hepatic stellate cell

LPS:

Lipopolysaccharide

LSEC:

Liver sinusoidal endothelial cell

MMPs:

Matrix metalloproteinases

OAH:

Ordinary adenomatous hyperplasia

PDGF:

Platelet-derived growth factor

PH:

Partial hepatectomy

TGF:

Transforming growth factor

VEGF:

Vascular endothelial growth factor

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Acknowledgements

We thank David Nadziejka of Van Andel Research Institute, Grand Rapids, Michigan, for technical editing of the manuscript. This work is funded by National Key Sci-Tech Special Project of China (No. 2008ZX10002-019).

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People’s Republic of China

    Ji-An Chen, Ming Shi, Jin-Qing Li & Chao-Nan Qian

  2. Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People’s Republic of China

    Ji-An Chen, Ming Shi & Jin-Qing Li

  3. NCCS-VARI Translational Research Laboratory, Humphrey-Oei Institute of Cancer Research, National Cancer Centre of Singapore, 11 Hospital Drive, Singapore, 169610, Singapore

    Chao-Nan Qian

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  1. Ji-An Chen
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  2. Ming Shi
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Correspondence to Chao-Nan Qian.

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Chen, JA., Shi, M., Li, JQ. et al. Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration. Hepatol Int 4, 537–547 (2010). https://doi.org/10.1007/s12072-010-9192-4

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  • DOI: https://doi.org/10.1007/s12072-010-9192-4

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