CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma

Wan-Hang Zhou; Yao Wang; Cong Yan; Wei-Dong Du; Maged Ali Al-Aroomi; Li Zheng; Shan-Feng Lin; Jia-Xing Gao; Sheng Jiang; Zeng-Xu Wang; Chang-Fu Sun; Fa-Yu Liu

doi:10.1007/s12672-022-00533-x

Discover Oncology (Jul 2022)

CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma

Wan-Hang Zhou,
Yao Wang,
Cong Yan,
Wei-Dong Du,
Maged Ali Al-Aroomi,
Li Zheng,
Shan-Feng Lin,
Jia-Xing Gao,
Sheng Jiang,
Zeng-Xu Wang,
Chang-Fu Sun,
Fa-Yu Liu

Affiliations

Wan-Hang Zhou: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Yao Wang: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Cong Yan: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Wei-Dong Du: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Maged Ali Al-Aroomi: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Li Zheng: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Shan-Feng Lin: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Jia-Xing Gao: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Sheng Jiang: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Zeng-Xu Wang: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Chang-Fu Sun: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning
Fa-Yu Liu: Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning

DOI: https://doi.org/10.1007/s12672-022-00533-x
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 15

Abstract

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Abstract Purpose This 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). Methods We 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. Results In 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. Conclusion CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

Published in Discover Oncology

ISSN: 2730-6011 (Online)
Publisher: Springer
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.springer.com/journal/12672/

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