Chiu Kuo-Chou, Lee Chien-Hsing, Liu Shyun-Yeu, Chou Yu-Ting, Huang Ren-Yeong, Huang Shih-Ming, Shieh Yi-Shing
Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Oral Oncol. 2015 Jul;51(7):683-9. doi: 10.1016/j.oraloncology.2015.04.004. Epub 2015 Apr 21.
This study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC).
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-κB were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues.
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-κB diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues.
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-κB pathway.
本研究调查了Axl信号通路在口腔鳞状细胞癌（OSCC）中肿瘤相关巨噬细胞（TAM）极化过程中的潜在作用。
收集OSCC细胞（OEC-M1和YD38）的条件培养基（CM），并检测其对巨噬细胞（THP-1）极化的影响。对Axl、PI3/Akt和NF-κB进行调控，以研究它们在TAM极化中的潜在作用。通过免疫组织化学分析OSCC组织中pAxl和CD206的表达。
用OSCC的CM处理后，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的表达增加。OSCC中激活的Axl信号通路增强了M2诱导能力。抑制Axl信号通路以及抑制PI3/Akt和NF-κB可减少M2诱导。在OSCC组织中，pAxl表达与CD206阳性细胞的分布显著相关。
OSCC的Axl信号通路参与将TAM极化为M2表型。OSCC细胞诱导M2表型巨噬细胞极化可能涉及Axl/PI3/Akt/NF-κB途径。
