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Review
. 2022 Aug 16;10(1):59.
doi: 10.1186/s40364-022-00406-z.

Advances of cancer-associated fibroblasts in liver cancer

Hao Peng #  1 , Erwei Zhu #  2 , Yewei Zhang  3
Affiliations
Review

Advances of cancer-associated fibroblasts in liver cancer

Hao Peng et al. Biomark Res. .

Abstract

Liver cancer is one of the most common malignant tumors worldwide, it is ranked sixth in incidence and fourth in mortality. According to the distinct origin of malignant tumor cells, liver cancer is mainly divided into hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Since most cases are diagnosed at an advanced stage, the prognosis of liver cancer is poor. Tumor growth depends on the dynamic interaction of various cellular components in the tumor microenvironment (TME). As the most abundant components of tumor stroma, cancer-associated fibroblasts (CAFs) have been involved in the progression of liver cancer. The interplay between CAFs and tumor cells, immune cells, or vascular endothelial cells in the TME through direct cell-to-cell contact or indirect paracrine interaction, affects the initiation and development of tumors. Additionally, CAFs are not a homogeneous cell population in liver cancer. Recently, single-cell sequencing technology has been used to help better understand the diversity of CAFs in liver cancer. In this review, we mainly update the knowledge of CAFs both in HCC and CCA, including their cell origins, chemoresistance, tumor stemness induction, tumor immune microenvironment formation, and the role of tumor cells on CAFs. Understanding the context-dependent role of different CAFs subsets provides new strategies for precise liver cancer treatment.

Keywords: CCA; HCC; Liver cancer; cancer-associated fibroblasts.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Morphological manifestations of fibroblasts in HCC. A CAFs and NFs extracted from HCC tissue and normal liver tissue were identified by immunofluorescence staining for α-SMA and Vimentin. CAFs exhibited more abundant cytoplasmic content than NFs. B Representative graphs showed two HCC cases with different α-SMA + CAFs distribution densities, with case1 exhibiting more rich CAFs infiltration relative to case2. Peng, H., R. Xue, Z. Ju, J. Qiu, J. Wang, W. Yan, et al., Ann Transl Med, 2020. 8(14): 856
Fig. 2
Fig. 2
The origin and the role of CAFs in liver cancer. Schematic illustration of potential cellular origins of CAFs, including epithelial cells, endothelial cells, tumor cells, HSCs, portal fibroblasts, and MSCs. The upper part of the picture shows the the influence exerted by CAFs in the TME, including chemoresistance, stemness induction, tumor immune, angiogenesis, and aggressiveness
See this image and copyright information in PMC

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