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Biochemistry (Moscow)

, Volume 82, Issue 8, pp 861–873 | Cite as

Components of the hepatocellular carcinoma microenvironment and their role in tumor progression

  • M. V. Novikova
  • N. V. Khromova
  • P. B. KopninEmail author
Review
  • 330 Downloads

Abstract

This review summarizes recently published data on the mechanisms of tumor cell interaction with the tumor microenvironment. Tumor stroma influences the processes of hepatocarcinogenesis, epithelial-to-mesenchymal transition, invasion, and metastasis. The tumor microenvironment includes both cellular and noncellular components. Main cellular components of hepatocellular carcinoma (HCC) stroma are tumor-associated fibroblasts, hepatic stellate cells, immune cells, and endothelial cells that produce extracellular components of tumor microenvironment such as extracellular matrix, various proteins, proteolytic enzymes, growth factors, and cytokines. The noncellular components of the stroma modulate signaling pathways in tumor cells and stimulate invasion and metastasis. The tumor microenvironment composition and organization can serve as prognostic factors in HCC pathogenesis. Current approaches in HCC targeted therapy are aimed at creating efficient strategies for interrupting tumor interactions with the stroma. Recent data on the composition and role of the microenvironment in HCC pathogenesis, as well as new developments in antitumor drug design are discussed.

Keywords

hepatocellular carcinoma tumor microenvironment cytokines hepatic stellate cells Kupffer cells cancer-associated fibroblasts extracellular matrix 

Abbreviations

CAFs

cancer-associated fibroblasts

ECM

extracellular matrix

EMT

epithelial-to-mesenchymal transition

HCC

hepatocellular carcinoma

HSCs

hepatic stellate cells

MMP

matrix metalloproteinases

TAMs

tumor-associated macrophages

TIMP

tissue inhibitor of metalloproteinases

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • M. V. Novikova
    • 1
  • N. V. Khromova
    • 1
  • P. B. Kopnin
    • 1
    Email author
  1. 1.Blokhin Russian Cancer Research CenterMinistry of Health of RussiaMoscowRussia

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