Hepatic Stellate Cells in Liver Tumor

  • Hidenori ShirahaEmail author
  • Masaya Iwamuro
  • Hiroyuki Okada
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1234)


Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are the most common types of primary liver cancers. Moreover, the liver is the second most frequently involved organ in cancer metastasis after lymph nodes. The tumor microenvironment is crucial for the development of both primary and secondary liver cancers. The hepatic microenvironment consists of multiple cell types, including liver sinusoidal endothelial cells, Kupffer cells, natural killer cells, liver-associated lymphocytes, and hepatic stellate cells (HSCs). The microenvironment of a normal liver changes to a tumor microenvironment when tumor cells exist or tumor cells migrate to and multiply in the liver. Interactions between tumor cells and non-transformed cells generate a tumor microenvironment that contributes significantly to tumor progression. HSCs play a central role in the tumor microenvironment crosstalk. As this crosstalk is crucial for liver carcinogenesis and liver-tumor development, elucidating the mechanism underlying the interaction of HSCs with the tumor microenvironment could provide potential therapeutic targets for liver cancer.


Extracellular matrix Matrix metalloproteinase Myofibroblast Cancer-associated fibroblast Tumor-infiltrating leukocyte Platelet-derived growth factor Transforming growth factor-β Epithelial-mesenchymal transition Vascular endothelial growth factor Tumor-associated macrophages Stromal cell-derived factor-1 Tumor stroma Jagged-1 Angiogenesis Fibroblast activation protein 



Cancer-associated fibroblasts


Chemokine (C-C motif) ligand 2


Extracellular matrix


Epithelial-mesenchymal transition


Fibroblast activation protein


Fibroblast growth factor

GI tract

Gastrointestinal tract


Hepatocellular carcinoma


Hepatocyte growth factor


Hepatic stellate cells


Intrahepatic cholangiocarcinoma


Insulin-like growth factor I




Liver sinusoidal endothelial cells


Monocyte chemoattractant protein 1


Myeloid-derived suppressor cells




Matrix metalloproteinases

NK cell

Natural killer cell




Platelet-derived growth factor


Stromal cell-derived factor-1


Tumor-associated macrophages


Transforming growth factor-β


Tumor-infiltrating leukocytes


Tissue inhibitors of matrix metalloproteinases


Regulatory T cells


Vascular endothelial growth factor


α-smooth muscle actin


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Hidenori Shiraha
    • 1
    Email author
  • Masaya Iwamuro
    • 1
  • Hiroyuki Okada
    • 1
  1. 1.Department of Gastroenterology and HepatologyOkayama University Faculty of MedicineOkayamaJapan

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