دورية أكاديمية
S100 calcium‐binding protein A9 from tumor‐associated macrophage enhances cancer stem cell‐like properties of hepatocellular carcinoma.
العنوان: | S100 calcium‐binding protein A9 from tumor‐associated macrophage enhances cancer stem cell‐like properties of hepatocellular carcinoma. |
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المؤلفون: | Wei, Ran, Zhu, Wen‐Wei, Yu, Guang‐Yang, Wang, Xuan, Gao, Chao, Zhou, Xu, Lin, Zhi‐Fei, Shao, Wei‐Qing, Wang, Sheng‐Hao, Lu, Ming, Qin, Lun‐Xiu |
المصدر: | International Journal of Cancer; Mar2021, Vol. 148 Issue 5, p1233-1244, 12p |
مصطلحات موضوعية: | CALCIUM-binding proteins, RECEPTOR for advanced glycation end products (RAGE), HEPATOCELLULAR carcinoma, NF-kappa B, MACROPHAGES, CARRIER proteins |
مستخلص: | Tumor‐associated macrophages (TAMs) are crucial components of the tumor microenvironment. They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP‐1 cells in vitro to investigate their functions in HCC progression. S100 calcium‐binding protein A9 (S100A9), an inflammatory microenvironment‐related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell‐like properties of HepG2 and MHCC‐97H cells by activating nuclear factor‐kappa B signaling pathway through advanced glycosylation end product‐specific receptor in a Ca2+‐dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC‐97H cells recruited more macrophages via chemokine (CC motif) ligand 2, which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate secreted protein S100A9 and enhance the stem cell‐like properties of HCC cells and provide a potential therapeutic target for combating HCC. What's new? Prognosis of hepatocellular carcinoma (HCC) is influenced by tumor‐associated macrophages (TAMs) in the tumor microenvironment. Little is known, however, about how TAMs fuel HCC progression. This comparative analysis of RNA‐sequencing and whole‐genome expression profiling between TAMs and nonactivated M0 macrophages identified three common upregulated genes with potential impact on HCC prognosis. Among them, S100 calcium binding protein A9 (S100A9) was found to enhance stem cell‐like properties in HCC cells, via Ca2+‐dependent signaling along the AGER/NF‐κB axis. Moreover, S100A9 increased TAM infiltration by facilitating CCL2 secretion. The findings warrant further investigation of S100A9 secretion and enhanced HCC cell stemness by TAMs. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: | Complementary Index |
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