Matrix metalloproteinase-21 promotes metastasis via increasing the recruitment and M2 polarization of macrophages in HCC.
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| Abstract |
MMP-21 is a newly identified member of the matrix metalloproteinase family and has been reported to regulate both embryonic development and tumor progression. However, the roles of MMP-21 in hemofiltrate C-C chemokine (HCC) remain largely unclear. In this study, we used western blot, qPCR and immunohistochemistry (IHC) to determine the upregulation of MMP-21 in HCC tissues, and showed that the increase in MMP-21 was associated with vascular invasion and poor prognosis. Although changing levels of MMP-21 in HCC cell lines had no significant effect on cell migration or invasion abilities in in vitro transwell tests, both IHC analysis and in vivo mouse models proved that upregulated MMP-21 promoted metastasis. Functional enrichments of MMP-21 using The Cancer Genome Atlas (TCGA) data suggested that MMP-21 might regulate metastasis via macrophages. Further experiments proved that MMP-21 enhanced macrophage recruitment by increasing CCL-14 levels and promoted M2-type polarization of macrophage by elevating the expression of CSF-1 and FGF-1. Taken together, this study revealed that MMP-21 controlled the tumor microenvironment remodeling and functional regulation of macrophages to regulate HCC metastasis.
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| Authors | Jiangfan Zhou, Li Liu, Xudong Hu, Rong Feng, Niannian Zhao, Li Zhang, Wenhao Hu, Jian Zhang, Shiyong Huang, Lin Liu, Wei Li, Yunfeng Shan, Jing Jin |
| Journal | Cancer science (Cancer Sci) Vol. 114 Issue 2 Pg. 423-435 (Feb 2023) ISSN: 1349-7006 [Electronic] England |
| PMID | 35398966 (Publication Type: Journal Article) |
| Copyright | © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
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