Author:
Zhou Wan-Hang,Wang Yao,Yan Cong,Du Wei-Dong,Al-Aroomi Maged Ali,Zheng Li,Lin Shan-Feng,Gao Jia-Xing,Jiang Sheng,Wang Zeng-Xu,Sun Chang-Fu,Liu Fa-Yu
Abstract
AbstractPurposeThis study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC).MethodsWe analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro.ResultsIn OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro.ConclusionCCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.
Funder
Liaoning Department of Education Research Foundation
Liaoning Science and Technology Program
Special Funds of “First-Class Universities and Disciplines of the World” Project
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Endocrine and Autonomic Systems,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism
Cited by
6 articles.
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