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CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338204/ https://www.ncbi.nlm.nih.gov/pubmed/35904690 http://dx.doi.org/10.1007/s12672-022-00533-x |
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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 |
author_facet | 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 |
author_sort | Zhou, Wan-Hang |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-022-00533-x. |
format | Online Article Text |
id | pubmed-9338204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-93382042022-07-31 CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma 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 Discov Oncol Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-022-00533-x. Springer US 2022-07-29 /pmc/articles/PMC9338204/ /pubmed/35904690 http://dx.doi.org/10.1007/s12672-022-00533-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research 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 CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma |
title | CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma |
title_full | CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma |
title_fullStr | CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma |
title_full_unstemmed | CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma |
title_short | CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma |
title_sort | cc chemokine receptor 7 promotes macrophage recruitment and induces m2-polarization through cc chemokine ligand 19&21 in oral squamous cell carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338204/ https://www.ncbi.nlm.nih.gov/pubmed/35904690 http://dx.doi.org/10.1007/s12672-022-00533-x |
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