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Review
. 2019 Sep 23;12(1):101.
doi: 10.1186/s13045-019-0782-x.

Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma

Zeli Yin  1   2   3 , Chengyong Dong  1   2   3 , Keqiu Jiang  1   2   3 , Zhe Xu  3 , Rui Li  1   2   3 , Kun Guo  4   5 , Shujuan Shao  6 , Liming Wang  7   8   9
Affiliations
Review

Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma

Zeli Yin et al. J Hematol Oncol. .

Abstract

Hepatocellular carcinoma (HCC) is a lethal disease, and recurrence and metastasis are the major causes of death in HCC patients. Cancer-associated fibroblasts (CAFs), a major stromal cell type in the HCC microenvironment, promote HCC progression, and have gradually become a hot research topic in HCC-targeted therapy. This review comprehensively describes and discusses the heterogeneous tissue distribution, cellular origin, phenotype, and biological functions of HCC-associated fibroblasts. Furthermore, the possible use of CAFs for predicting HCC prognosis and in targeted therapeutic strategies is discussed, highlighting the critical roles of CAFs in HCC progression, diagnosis, and therapy.

Keywords: Cancer-associated fibroblasts (CAFs); Hepatocellular carcinoma (HCC); Tumor microenvironment (TME).

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The distribution of α-SMA-positive CAFs in HCC tissues. a CAFs located in the tumor fibrous capsule (× 100). b CAFs located in the tumor fibrous septum (× 200). c–d HCC cells positive for α-SMA expression (× 200, × 400, respectively). e–f CAFs in the blood sinus (× 200, × 400, respectively)
Fig. 2
Fig. 2
Heterogeneous cellular origins of CAFs. CAFs in the HCC microenvironment may be derived from HCC cells, HSCs, MSCs, and HSECs. Hypoxia and TGF-β can induce EMT and expression of α-SMA and FAP in HCC cells. HSCs can differentiate into CAFs under stimulation with CM or exosomal miRNA-21 secreted by HCC cells. CM generated from HCC cells can also induce the expression of tenascin-C and SDF-1 in MSCs. HSECs are a potential cellular origin of CAFs in the HCC microenvironment
See this image and copyright information in PMC

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet (London, England) 2018;391(10125):1023–1075. doi: 10.1016/S0140-6736(17)33326-3. - DOI - PMC - PubMed
    1. Erstad DJ, Tanabe KK. Prognostic and therapeutic implications of microvascular invasion in hepatocellular carcinoma. Ann Surg Oncol. 2019;26:1474–1493. doi: 10.1245/s10434-019-07227-9. - DOI - PubMed
    1. EbioMedicine The tumor microenvironment: a druggable target for metastatic disease? EBioMedicine. 2018;31:1–2. doi: 10.1016/j.ebiom.2018.05.005. - DOI - PMC - PubMed
    1. Neesse A, Bauer CA, Ohlund D. Stromal biology and therapy in pancreatic cancer: ready for clinical translation? Gut. 2019;68(1):159–171. doi: 10.1136/gutjnl-2018-316451. - DOI - PubMed

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