Kif4A mediate the accumulation and reeducation of THP-1 derived macrophages via regulation of CCL2-CCR2 expression in crosstalking with OSCC

• Published in: Scientific reports Vol. 7; no. 1; pp. 2226 - 12
• Main Authors: Zhang, Yun, Liu, Shaohua, Qu, Daiwei, Wang, Ketao, Zhang, Lin, Jing, Xuanxuan, Li, Chen, Wei, Fengcai, Qu, Xun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/109; 13/21; 13/31; 13/89; 38/77; 631/250/580; 631/67/327; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CCR2 protein; Cell Communication - genetics; Cell Line, Tumor; Cells, Cultured; Chemokine CCL2 - genetics; Coculture Techniques; Cytokines - metabolism; Gene Expression Regulation, Neoplastic; Growth factors; Humanities and Social Sciences; Humans; Immunological tolerance; Kinesin; Kinesin - genetics; Ligands; Macrophages; Macrophages - metabolism; Metastases; Metastasis; Monocyte chemoattractant protein 1; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; multidisciplinary; Oral carcinoma; Oral squamous cell carcinoma; Receptors, CCR2 - genetics; Recruitment; Science; Science (multidisciplinary); Signal Transduction; siRNA; Squamous cell carcinoma; STAT3 Transcription Factor - metabolism; Tumor cells; Tumorigenesis
• ISSN: 2045-2322; 2045-2322
• 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.