Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages.
Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages.
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DOI：
10.1158/0008-5472.can-13-2689
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发表时间：
2014-06-01
期刊：
影响因子：
11.2
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Zhang Y;Sun Y;Rao E;Yan F;Li Q;Zhang Y;Silverstein KA;Liu S;Sauter E;Cleary MP;Li B
脂肪酸结合蛋白(FABP)是已知的代谢和炎症途径的中心调节者，但它们在肿瘤发展中的作用在很大程度上仍未被探索。在这里，我们报告了宿主表达的表皮FABP(E-FABP)对乳腺肿瘤的生长具有保护作用。我们发现E-FABP在巨噬细胞中高表达，特别是在特定的亚群中，促进了它们的抗肿瘤活性。在肿瘤间质中，表达E-FABP的肿瘤相关巨噬细胞(TAM)通过上调脂滴(LD)的形成来产生高水平的干扰素β(干扰素β)。E-FABP介导的干扰素β信号可以进一步增强肿瘤杀伤效应细胞，特别是NK细胞在肿瘤基质中的募集，以发挥抗肿瘤活性。这些发现证实E-FABP是一种新的保护因子，可以增强干扰素β对肿瘤生长的反应。
Fatty acid binding proteins (FABPs) are known central regulators of both metabolic and inflammatory pathways, but their role in tumor development remains largely unexplored. Here, we report that host expression of epidermal FABP (E-FABP) protects against mammary tumor growth. We find that E-FABP is highly expressed in macrophages, particularly in a specific subset, promoting their antitumor activity. In the tumor stroma E-FABP-expressing tumor-associated macrophages (TAMs) produce high levels of interferon β (IFNβ) through upregulation of lipid droplet (LD) formation in response to tumors. E-FABP-mediated IFNβ signaling can further enhance recruitment of tumoricidal effector cells, in particular NK cells, to the tumor stroma for antitumor activity. These findings identify E-FABP as a new protective factor to strengthen IFNβ responses against tumor growth.