Journal
BIOCHEMISTRY-MOSCOW
Volume 82, Issue 8, Pages 861-873Publisher
MAIK NAUKA/INTERPERIODICA/SPRINGER
DOI: 10.1134/S0006297917080016
Keywords
hepatocellular carcinoma; tumor microenvironment; cytokines; hepatic stellate cells; Kupffer cells; cancer-associated fibroblasts; extracellular matrix
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Funding
- Russian Science Foundation [14-15-00467]
- Russian Science Foundation [17-15-00046] Funding Source: Russian Science Foundation
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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.
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