Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer.
Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer.
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Interleukin-17 和前列腺素 E2 参与肺癌中 M2 巨噬细胞主导的微环境的形成
DOI：
10.1097/jto.0b013e3182542752
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
You Z
中科院分区：
文献类型：
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作者：
Liu L;Ge D;Ma L;Mei J;Liu S;Zhang Q;Ren F;Liao H;Pu Q;Wang T;You Z
肿瘤相关巨噬细胞（TAM）分为 M1 和 M2 巨噬细胞。 M1巨噬细胞抑制肿瘤生长，而M2巨噬细胞促进肿瘤生长和转移。本研究的目的是研究导致非小细胞肺癌中M2巨噬细胞主导的肿瘤微环境形成的可能原因。使用免疫组织化学染色检查了 48 个存档的肺肿瘤样本中白介素 17 (IL-17) 受体 IL-17RA 和 IL-17RC 的表达以及 TAM 的数量。使用酶联免疫吸附测定 (ELISA) 和蛋白质印迹分析检查 20 个新鲜肺肿瘤和匹配的正常肺组织的 IL-17、环氧合酶-2 和前列腺素 E2 的表达。使用新鲜肺肿瘤组织和IL-17作为趋化剂进行巨噬细胞迁移测定。使用实时定量聚合酶链反应分析 M2 巨噬细胞分化的诱导。 TAM 表达 IL-17RA 和 IL-17RC。与正常肺组织相比，肺肿瘤表达更高水平的 IL-17、环氧合酶-2 和前列腺素 E2。肺肿瘤组织通过IL-17吸引小鼠RAW264.7巨噬细胞和原代腹膜巨噬细胞的迁移，这是由IL-17RA和IL-17RC介导的。 IL-17 不诱导 M1 或 M2 巨噬细胞分化。然而，当两种细胞系共培养时，人肺癌A549细胞强烈诱导RAW264.7巨噬细胞的M2巨噬细胞分化。鉴定A549细胞分泌的诱导因子为前列腺素E2。 IL-17招募巨噬细胞，前列腺素E2诱导M2巨噬细胞分化，因此肺癌中IL-17和前列腺素E2水平的增加有助于形成M2巨噬细胞主导的肿瘤微环境。
Tumor-associated macrophages (TAMs) are divided into M1 and M2 macrophages. M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth and metastasis. The aim of this study was to study the possible causes leading to formation of an M2 macrophage-dominant tumor microenvironment in non-small cell lung cancer. Forty-eight archived lung tumor samples were examined for expression of interleukin-17 (IL-17) receptors IL-17RA and IL-17RC and the number of TAMs using immunohistochemical staining. Twenty fresh lung tumors and matched normal lung tissues were examined for expression of IL-17, cyclooxygenase-2, and prostaglandin E2, using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Macrophage migration assays were performed using fresh lung tumor tissues and IL-17 as chemoattractants. Induction of M2 macrophage differentiation was analyzed using real-time quantitative polymerase chain reaction. TAMs expressed IL-17RA and IL-17RC. Lung tumors expressed higher levels of IL-17, cyclooxygenase-2, and prostaglandin E2, compared to normal lung tissues. Lung tumor tissues attracted migration of mouse RAW264.7 macrophages and primary peritoneal macrophages through IL-17, which was mediated by IL-17RA and IL-17RC. IL-17 did not induce either M1 or M2 macrophage differentiation. However, human lung cancer A549 cells strongly induced M2 macrophage differentiation of RAW264.7 macrophages when the two cell lines were co-cultured. The inductive factor secreted by A549 cells was identified to be prostaglandin E2. IL-17 recruits macrophages and prostaglandin E2 induces M2 macrophage differentiation, hence the increased levels of IL-17 and prostaglandin E2 in lung cancer contribute to formation of an M2 macrophage-dominant tumor microenvironment.