Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule
M2 tumor-associated macrophages (TAMs) have been a well-established promoter of oral squamous cell carcinoma (OSCC) progression. However, the mechanisms of M2 TAMs promoting OSCC metastasis have not been elucidated clearly. This study illustrated the regulatory mechanisms in which M2 TAMs enhance OS...
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/20/5081 |
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| author | Zhixin Liu Tao Rui Zhaoyu Lin Shule Xie Bin Zhou Min Fu Lianxi Mai Chuandong Zhu Guotao Wu Youyuan Wang |
| author_facet | Zhixin Liu Tao Rui Zhaoyu Lin Shule Xie Bin Zhou Min Fu Lianxi Mai Chuandong Zhu Guotao Wu Youyuan Wang |
| author_sort | Zhixin Liu |
| collection | DOAJ |
| description | M2 tumor-associated macrophages (TAMs) have been a well-established promoter of oral squamous cell carcinoma (OSCC) progression. However, the mechanisms of M2 TAMs promoting OSCC metastasis have not been elucidated clearly. This study illustrated the regulatory mechanisms in which M2 TAMs enhance OSCC malignancy in a novel point of view. In this study, mass spectrometry was utilized to analyze the proteins expression profile of M2 type monocyte-derived macrophages (MDMs-M2), whose results revealed the high expression of G3BP1 in M2 macrophages. RNA sequencing analyzed the genome-wide changes upon G3BP1 knockdown in MDMs-M2 and identified that CCL13 was the most significantly downregulated inflammatory cytokines in MDMs-M2. Co-immunoprecipitation and qualitative mass spectrometry were used to identify the proteins that directly interacted with endogenous G3BP1 in MDMs-M2. Elevated stress granule (SG) formation in stressed M2 TAMs enhanced the expression of CCL13, which promoted OSCC metastasis both in vitro and in vivo. For mechanisms, we demonstrated SG formation improved DDX3Y/hnRNPF-mediated CCL13 mRNA stability, thus enhancing CCL13 expression and promoting OSCC metastasis. Collectively, our findings demonstrated for the first time the roles of CCL13 in improving OSCC metastasis and illustrated the molecular mechanisms of CCL13 expression regulated by SG, indicating that the SG-CCL13 axis can be the potential targets for TAM-navigated tumor therapy. |
| first_indexed | 2024-03-09T20:32:35Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:32:35Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ee67f1fa9b8e4c59be1b1347f74bf19c2023-11-23T23:21:37ZengMDPI AGCancers2072-66942022-10-011420508110.3390/cancers14205081Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress GranuleZhixin Liu0Tao Rui1Zhaoyu Lin2Shule Xie3Bin Zhou4Min Fu5Lianxi Mai6Chuandong Zhu7Guotao Wu8Youyuan Wang9Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliate Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, 31 Huangsha Avenue, Guangzhou 510000, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, ChinaM2 tumor-associated macrophages (TAMs) have been a well-established promoter of oral squamous cell carcinoma (OSCC) progression. However, the mechanisms of M2 TAMs promoting OSCC metastasis have not been elucidated clearly. This study illustrated the regulatory mechanisms in which M2 TAMs enhance OSCC malignancy in a novel point of view. In this study, mass spectrometry was utilized to analyze the proteins expression profile of M2 type monocyte-derived macrophages (MDMs-M2), whose results revealed the high expression of G3BP1 in M2 macrophages. RNA sequencing analyzed the genome-wide changes upon G3BP1 knockdown in MDMs-M2 and identified that CCL13 was the most significantly downregulated inflammatory cytokines in MDMs-M2. Co-immunoprecipitation and qualitative mass spectrometry were used to identify the proteins that directly interacted with endogenous G3BP1 in MDMs-M2. Elevated stress granule (SG) formation in stressed M2 TAMs enhanced the expression of CCL13, which promoted OSCC metastasis both in vitro and in vivo. For mechanisms, we demonstrated SG formation improved DDX3Y/hnRNPF-mediated CCL13 mRNA stability, thus enhancing CCL13 expression and promoting OSCC metastasis. Collectively, our findings demonstrated for the first time the roles of CCL13 in improving OSCC metastasis and illustrated the molecular mechanisms of CCL13 expression regulated by SG, indicating that the SG-CCL13 axis can be the potential targets for TAM-navigated tumor therapy.https://www.mdpi.com/2072-6694/14/20/5081tumor-associated macrophageOSCC metastasisstress granuleCCL13mRNA stability |
| spellingShingle | Zhixin Liu Tao Rui Zhaoyu Lin Shule Xie Bin Zhou Min Fu Lianxi Mai Chuandong Zhu Guotao Wu Youyuan Wang Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule Cancers tumor-associated macrophage OSCC metastasis stress granule CCL13 mRNA stability |
| title | Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule |
| title_full | Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule |
| title_fullStr | Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule |
| title_full_unstemmed | Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule |
| title_short | Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule |
| title_sort | tumor associated macrophages promote metastasis of oral squamous cell carcinoma via ccl13 regulated by stress granule |
| topic | tumor-associated macrophage OSCC metastasis stress granule CCL13 mRNA stability |
| url | https://www.mdpi.com/2072-6694/14/20/5081 |
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