Increased B3GALNT2 in hepatocellular carcinoma promotes macrophage recruitment via reducing acetoacetate secretion and elevating MIF activity.
Increased B3GALNT2 in hepatocellular carcinoma promotes macrophage recruitment via reducing acetoacetate secretion and elevating MIF activity.
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肝细胞癌中 B3GALNT2 的增加通过减少乙酰乙酸分泌和提高 MIF 活性来促进巨噬细胞募集
DOI：
10.1186/s13045-018-0595-3
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发表时间：
2018-04-04
影响因子：
28.5
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Yang T;Wang Y;Dai W;Zheng X;Wang J;Song S;Fang L;Zhou J;Wu W;Gu J
肝细胞癌（Hepatocellular carcinoma，HCC）是世界上第六大恶性肿瘤，也是第三大肿瘤相关死亡原因，因此寻找有效的标志物和治疗靶点成为当务之急。β-1，3-N-乙酰氨基半乳糖基转移酶II（B3 GALNT 2）属于β-1，3-糖基转移酶（b3 GT）家族，在正常组织和肿瘤组织的生长发育中起重要作用。然而，关于B3 GALNT 2在肿瘤中的功能的研究相当有限。在这里，我们研究了B3 GALNT 2在HCC进展中的潜在作用。进行Western印迹、qPCR和免疫组织化学测定以定量HCC中B3 GALNT 2的相对表达。在肝癌细胞系和裸鼠中评估B3 GALNT 2在肿瘤进展中的功能。应用代谢组学分析来检测交替表达的小分子。采用酶活性测定法测定巨噬细胞抑制因子（MIF）的互变异构酶活性。对于表达分析，与邻近的正常组织相比，在肿瘤组织中观察到更高水平的B3 GALNT 2，并且B3 GALNT 2的上调与肿瘤大小增加和总生存率降低相关。B3 GALNT 2水平的改变并不影响体外细胞活力，但通过增强体内巨噬细胞募集促进肿瘤生长。此外，乙酰乙酸被鉴定为B3 GALNT 2介导的巨噬细胞募集中的关键分子。从机制上讲，B3 GALNT 2下调参与乙酰乙酸相关代谢的酶的表达，乙酰乙酸的减少恢复了MIF活性，从而促进了巨噬细胞的募集。本研究评估了B3 GALNT 2作为HCC肿瘤标志物的作用，并揭示了B3 GALNT 2在HCC代谢转化和微环境重塑中的功能。从机制上讲，B3 GALNT 2减少了一些代谢酶的表达，从而下调了乙酰乙酸的分泌水平。这减轻了MIF的活性并增强了巨噬细胞募集以促进肿瘤生长。本文的在线版本（10.1186/s13045-018-0595-3）包含补充材料，可供授权用户使用。
Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer and the third leading cause of tumor-related death, so it is urgently needed to discover efficient markers and targets for therapy. β-1,3-N-acetylgalactosaminyltransferase II (B3GALNT2) belongs to the β-1,3-glycosyltransferases (b3GT) family and has been reported to regulate development of both normal and tumor tissues. However, studies on the functions of B3GALNT2 in cancer are quite limited. Here we investigated the potential role of B3GALNT2 in HCC progression. Western blot, qPCR, and immunohistochemistry assays were performed to quantify the relative expression of B3GALNT2 in HCC. The functions of B3GALNT2 in tumor progression were evaluated in HCC cell lines and nude mice. Metabolomics analysis was applied to detect alternatively expressed small molecules. Enzyme activity assays were employed to determine the tautomerase activity of macrophage inhibitory factor (MIF). For expression analysis, higher levels of B3GALNT2 were observed in tumor tissues compared with adjacent normal tissues, and upregulation of B3GALNT2 correlated with increased tumor size and worse overall survival. Changing levels of B3GALNT2 did not influence cell viability in vitro but promoted tumor growth via enhancing macrophage recruitment in vivo. Furthermore, acetoacetate was identified as a key molecule in B3GALNT2-mediated macrophage recruitment. Mechanistically, B3GALNT2 downregulated expression of enzymes involved in acetoacetate-related metabolism, and reduction of acetoacetate revived MIF activity, thus promoting macrophage recruitment. This study evaluated B3GALNT2 as a tumor marker in HCC and revealed functions of B3GALNT2 in metabolic transformation and microenvironmental remodeling in HCC. Mechanistically, B3GALNT2 reduced expression of some metabolic enzymes and thus downregulated levels of secreted acetoacetate. This relieved the activity of MIF and enhanced macrophage recruitment to promote tumor growth. The online version of this article (10.1186/s13045-018-0595-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.3
作者：
BRISCOE, DA;FISKUM, G;KELLEHER, JK
通讯作者：
KELLEHER, JK
肿瘤招募的M2巨噬细胞通过M2巨噬细胞分泌的CHI3L1蛋白促进胃癌和乳腺癌转移
影响因子：
28.5
作者：
Chen Y;Zhang S;Wang Q;Zhang X
通讯作者：
Zhang X
DOI：
10.1038/icb.1979.54
发表时间：
1979-01-01
期刊：
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE
影响因子：
--
作者：
MAGEE, BA;POTEZNY, N;CONYERS, RAJ
通讯作者：
CONYERS, RAJ
影响因子：
56.9
作者：
BLOOM, BR;BENNETT, B
通讯作者：
BENNETT, B
影响因子：
4.4
作者：
Gregory, Julia L.;Morand, Eric F.;Hickey, Michael J.
通讯作者：
Hickey, Michael J.