Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma
Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2015.04.004
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发表时间：
2015-07-01
期刊：
影响因子：
4.8
通讯作者：
Shieh, Yi-Shing
中科院分区：
文献类型：
--
作者：
Chiu, Kuo-Chou;Lee, Chien-Hsing;Shieh, Yi-Shing
背景：本研究调查了 Axl 信号传导在口腔鳞状细胞癌 (OSCC) 肿瘤相关巨噬细胞 (TAM) 极化中的潜在参与。方法：收集 OSCC 细胞（OEC-M1 和 YD38）的条件培养基（CM），并检查其对巨噬细胞（THP-1）极化的影响。对 Axl、PI3/Akt 和 NF-kappa B 进行调节以研究它们在 TAM 极化中的潜在参与。采用免疫组织化学法分析口腔鳞癌组织中pAxl和CD206的表达。结果：口腔鳞癌CM治疗后，THP-1极化为M2表型，白细胞介素、血管内皮生长因子、基质金属蛋白酶和CD206表达增加。 OSCC 中激活的 Axl 信号传导增强了 M2 诱导能力。抑制 Axl 信号传导以及抑制 PI3/Akt 和 NF-κ B 可减少 M2 诱导。 pAxl表达与OSCC组织中CD206阳性细胞的分布显着相关。结论：OSCC的Axl信号传导参与将TAM向M2表型极化。 OSCC 细胞诱导 M2 表型巨噬细胞极化可能涉及 Axl/PI3/Akt/NF-kappa B 途径。 (C) 2015 Elsevier Ltd. 保留所有权利。
Background: This study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC).Methods: Condition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects on macrophage (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-kappa B were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues.Results: THP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-kappa B diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues.Conclusion: Axl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-kappa B pathway. (C) 2015 Elsevier Ltd. All rights reserved.