AUTHOR=Jia Wentao , Liang Shufang , Cheng Binbin , Ling Changquan 

TITLE=The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.763519

DOI=10.3389/fonc.2021.763519

ISSN=2234-943X

ABSTRACT=Invasion and metastasis are the main reasons for the high mortality of liver cancer, which involve the interaction of tumor stromal cells and malignant cells. Tumor associated fibroblasts (CAFs) are one of the major constituents of tumor stromal cells affecting tumor growth, invasion, and metastasis. The heterogeneous property and source of CAFs make both tumor-supporting and tumor-suppression effects possible. The mechanism for CAFs in supporting HCC progression can be categorized into the upregulated aggressiveness and stemness, the transformed metabolism towards glycolysis and glutamine reductive carboxylation, the polarized tumor immunity towards immune escape of HCC cells, and the increased angiogenesis. The tumor suppressive effect of fibroblasts highlights the functional heterogenicity of CAFs populations and provides new insights into tumor-stromal interplay mechanisms. In this review, we introduced several key inflammatory signaling pathways in the transformation of CAFs from normal stromal cells, and the heterogeneous biofunction of activated CAFs. In view of the pleiotropic regulation property of traditional Chinese medicine (TCM) and heterogeneous effect of CAFs, we also introduced the application and values of TCM in the treatment of HCC through targeting CAFs.