TY - JOUR
T1 - The tumor microenvironment in hepatocellular carcinoma
T2 - Current status and therapeutic targets
AU - Yang, Ju Dong
AU - Nakamura, Ikuo
AU - Roberts, Lewis R.
N1 - Funding Information:
Grant support: This work was supported by NIH grants CA100882 and CA128633 to LRR .
PY - 2011/2
Y1 - 2011/2
N2 - A growing body of literature highlights the cross-talk between tumor cells and the surrounding peri-tumoral stroma as a key modulator of the processes of hepatocarcinogenesis, epithelial mesenchymal transition (EMT), tumor invasion and metastasis. The tumor microenvironment can be broadly classified into cellular and non-cellular components. The major cellular components include hepatic stellate cells, fibroblasts, immune, and endothelial cells. These cell types produce the non-cellular components of the tumor stroma, including extracellular matrix (ECM) proteins, proteolytic enzymes, growth factors and inflammatory cytokines. The non-cellular component of the tumor stroma modulates hepatocellular carcinoma (HCC) biology by effects on cancer signaling pathways in tumor cells and on tumor invasion and metastasis. Global gene expression profiling of HCC has revealed that the tumor microenvironment is an important component in the biologic and prognostic classification of HCC. There are substantial efforts underway to develop novel drugs targeting tumor-stromal interactions. In this review, we discuss the current knowledge about the role of the tumor microenvironment in pathogenesis of HCC, the role of the tumor microenvironment in the classification of HCC and efforts to develop treatments targeting the tumor microenvironment.
AB - A growing body of literature highlights the cross-talk between tumor cells and the surrounding peri-tumoral stroma as a key modulator of the processes of hepatocarcinogenesis, epithelial mesenchymal transition (EMT), tumor invasion and metastasis. The tumor microenvironment can be broadly classified into cellular and non-cellular components. The major cellular components include hepatic stellate cells, fibroblasts, immune, and endothelial cells. These cell types produce the non-cellular components of the tumor stroma, including extracellular matrix (ECM) proteins, proteolytic enzymes, growth factors and inflammatory cytokines. The non-cellular component of the tumor stroma modulates hepatocellular carcinoma (HCC) biology by effects on cancer signaling pathways in tumor cells and on tumor invasion and metastasis. Global gene expression profiling of HCC has revealed that the tumor microenvironment is an important component in the biologic and prognostic classification of HCC. There are substantial efforts underway to develop novel drugs targeting tumor-stromal interactions. In this review, we discuss the current knowledge about the role of the tumor microenvironment in pathogenesis of HCC, the role of the tumor microenvironment in the classification of HCC and efforts to develop treatments targeting the tumor microenvironment.
KW - Cancer-associated fibroblast
KW - Gene signature
KW - Hepatic stellate cells
KW - Hepatocellular carcinoma
KW - Inflammatory cytokine
KW - Kupffer cell
KW - Matrix metalloproteinase
KW - T cell
KW - TGF-β1
KW - Tissue inhibitor of metalloproteinase
KW - Treatment
KW - Tumor microenvironment
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U2 - 10.1016/j.semcancer.2010.10.007
DO - 10.1016/j.semcancer.2010.10.007
M3 - Review article
C2 - 20946957
AN - SCOPUS:79952038728
SN - 1044-579X
VL - 21
SP - 35
EP - 43
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
IS - 1
ER -