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ID 117319
Title Alternative
CAF-INDUCED TAMs PROMOTE HCC PROGRESSION VIA PAI-1
Author
Chen, Shuhai Tokushima University
Tokuda, Kazunori Tokushima University
Keywords
tumor‑associated macrophages
cancer‑associated fibroblasts
hepatocellular carcinoma
plasminogen activator inhibitor‑1
epithelial‑mesenchymal transition
Content Type
Journal Article
Description
Targeting the tumor stroma is an important strategy in cancer treatment. Cancer‑associated fibroblasts (CAFs) and tumor‑associated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor‑1 (PAI‑1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI‑1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells in vitro. It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL‑6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI‑1 expression was upregulated in TAMs after being stimulated with CAF‑conditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelial‑mesenchymal transition. CAFs were the main producer of C‑X‑C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI‑1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI‑1 secretion via CXCL12. Furthermore, it was found that PAI‑1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.
Journal Title
International Journal of Oncology
ISSN
10196439
17912423
NCID
AA10992511
Publisher
Spandidos Publications
Volume
59
Issue
2
Start Page
59
Published Date
2021-07-01
Rights
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences
University Hospital