Institute of Stomatology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P.R. China.
Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P.R. China.
Sci Rep. 2017 May 22;7(1):2226. doi: 10.1038/s41598-017-02261-7.
Crosstalk between tumor infiltrating macrophages and tumor cells is thought to play an indispensable role in oral squamous cell carcinomas (OSCC) by induction and maintenance of tolerance microenvironment. High infiltration of M2 macrophages and increasing expression of Kinesin family member 4A (Kif4A) in primary OSCC have been proved to correlate with greater tumoral size and poor clinical outcome. However, linkage between Kif4A and infiltrating macrophages in tumorigenesis and progression remains unclear. In the present study, we show that, the interaction between THP-1derived macrophage and OSCC cell line Cal-27 may up-regulate the Kif4A expression in both of them. Additionally, elevated soluble CCL2 in medium and more expression of CCR2 on macrophage were observed during the crosstalk. SiRNA of Kif4A and neutralizing antibody of CCL2 were utilized to identify that; increasing Kif4A can promote the recruitment of macrophages towards Cal-27 and educate them to M2 polarized macrophages via regulating CCL2/CCR2. In combination, the results of the present study may provide interesting clues to understanding the Kif4A-CCL2/CCR2-macrophage axis as a novel therapeutic target to improve the clinical outcome of OSCC.
肿瘤浸润巨噬细胞与肿瘤细胞之间的串扰被认为通过诱导和维持耐受微环境在口腔鳞状细胞癌（OSCC）中发挥不可或缺的作用。大量浸润的 M2 巨噬细胞和原发性 OSCC 中 Kinesin 家族成员 4A（Kif4A）的表达增加已被证明与更大的肿瘤大小和不良的临床结果相关。然而，Kif4A 与肿瘤发生和进展中的浸润巨噬细胞之间的联系仍不清楚。在本研究中，我们表明，THP-1 衍生的巨噬细胞与 OSCC 细胞系 Cal-27 之间的相互作用可能会上调它们两者中的 Kif4A 表达。此外，在串扰过程中观察到培养基中可溶性 CCL2 的升高和巨噬细胞上 CCR2 的更多表达。利用 Kif4A 的 siRNA 和 CCL2 的中和抗体来鉴定：增加 Kif4A 可以通过调节 CCL2/CCR2 促进巨噬细胞向 Cal-27 的募集，并将其诱导为 M2 极化的巨噬细胞。综上所述，本研究的结果可能为理解 Kif4A-CCL2/CCR2-巨噬细胞轴作为改善 OSCC 临床结果的新治疗靶点提供有趣的线索。
