CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma
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 asso...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2022-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-022-00533-x |
| _version_ | 1818162609047732224 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Wan-Hang Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T16:36:23Z |
| format | Article |
| id | doaj.art-aa38f1c11f2b483d8d436463c5cf793e |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-12-11T16:36:23Z |
| publishDate | 2022-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-aa38f1c11f2b483d8d436463c5cf793e2022-12-22T00:58:27ZengSpringerDiscover Oncology2730-60112022-07-0113111510.1007/s12672-022-00533-xCC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinomaWan-Hang Zhou0Yao Wang1Cong Yan2Wei-Dong Du3Maged Ali Al-Aroomi4Li Zheng5Shan-Feng Lin6Jia-Xing Gao7Sheng Jiang8Zeng-Xu Wang9Chang-Fu Sun10Fa-Yu Liu11Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningDepartment of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of LiaoningAbstract 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.https://doi.org/10.1007/s12672-022-00533-xCCR7MacrophageRecruitmentPolarizationOral squamous cell carcinoma |
| spellingShingle | 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 CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma Discover Oncology CCR7 Macrophage Recruitment Polarization 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 | CCR7 Macrophage Recruitment Polarization Oral squamous cell carcinoma |
| url | https://doi.org/10.1007/s12672-022-00533-x |
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