Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth
Abstract Tumor-associated macrophages (TAMs) account for 30–50% of glioma microenvironment. The interaction between glioma tumor cells and TAMs can promote tumor progression, but the intrinsic mechanisms remain unclear. Herein, we reported that soluble LRIG3 (sLRIG3) derived from glioma tumor cells...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05555-z |
| _version_ | 1797952375178133504 |
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| author | Youwei Li Wei Wang Xiaoshuang Hou Wenda Huang Po Zhang Yue He Baofeng Wang Qiuhong Duan Feng Mao Dongsheng Guo |
| author_facet | Youwei Li Wei Wang Xiaoshuang Hou Wenda Huang Po Zhang Yue He Baofeng Wang Qiuhong Duan Feng Mao Dongsheng Guo |
| author_sort | Youwei Li |
| collection | DOAJ |
| description | Abstract Tumor-associated macrophages (TAMs) account for 30–50% of glioma microenvironment. The interaction between glioma tumor cells and TAMs can promote tumor progression, but the intrinsic mechanisms remain unclear. Herein, we reported that soluble LRIG3 (sLRIG3) derived from glioma tumor cells can block the M2 polarization of TAMs via interacting with NETO2, thus suppressing GBM malignant progression. The expression or activity of ADAM17 in glioma cells was positively correlated with the expression of sLRIG3 in cell supernatant. Soluble LRIG3 can suppress the M2-like polarity transformation of TAMs and inhibit the growth of tumor. High expression of LRIG3 predicts a good prognosis in patients with glioma. Mass spectrometry and Co-immunoprecipitation showed that sLRIG3 interacts with the CUB1 domain of NETO2 in TAMs. Silencing or knockout of NETO2 could block the effect of sLRIG3, which inhibited the M2-like polarity transformation of TAMs and promoted GBM tumor growth. However, overexpressing His-target NETO2 with CUB1 deletion mutation does not fully recover the suppressive effects of sLRIG3 on the TAM M2-polarization in NETO2-Knockout TAMs. Our study revealed vital molecular crosstalk between GBM tumor cells and TAMs. Glioma cells mediated the M2 polarization of TAM through the sLRIG3-NETO2 pathway and inhibited the progression of GBM, suggesting that sLRIG3-NETO2 may be a potential target for GBM treatment. |
| first_indexed | 2024-04-10T22:45:20Z |
| format | Article |
| id | doaj.art-d00b1eacc135468e8c612aa768ff18df |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-10T22:45:20Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-d00b1eacc135468e8c612aa768ff18df2023-01-15T12:22:37ZengNature Publishing GroupCell Death and Disease2041-48892023-01-0114111510.1038/s41419-023-05555-zGlioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growthYouwei Li0Wei Wang1Xiaoshuang Hou2Wenda Huang3Po Zhang4Yue He5Baofeng Wang6Qiuhong Duan7Feng Mao8Dongsheng Guo9Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Tumor-associated macrophages (TAMs) account for 30–50% of glioma microenvironment. The interaction between glioma tumor cells and TAMs can promote tumor progression, but the intrinsic mechanisms remain unclear. Herein, we reported that soluble LRIG3 (sLRIG3) derived from glioma tumor cells can block the M2 polarization of TAMs via interacting with NETO2, thus suppressing GBM malignant progression. The expression or activity of ADAM17 in glioma cells was positively correlated with the expression of sLRIG3 in cell supernatant. Soluble LRIG3 can suppress the M2-like polarity transformation of TAMs and inhibit the growth of tumor. High expression of LRIG3 predicts a good prognosis in patients with glioma. Mass spectrometry and Co-immunoprecipitation showed that sLRIG3 interacts with the CUB1 domain of NETO2 in TAMs. Silencing or knockout of NETO2 could block the effect of sLRIG3, which inhibited the M2-like polarity transformation of TAMs and promoted GBM tumor growth. However, overexpressing His-target NETO2 with CUB1 deletion mutation does not fully recover the suppressive effects of sLRIG3 on the TAM M2-polarization in NETO2-Knockout TAMs. Our study revealed vital molecular crosstalk between GBM tumor cells and TAMs. Glioma cells mediated the M2 polarization of TAM through the sLRIG3-NETO2 pathway and inhibited the progression of GBM, suggesting that sLRIG3-NETO2 may be a potential target for GBM treatment.https://doi.org/10.1038/s41419-023-05555-z |
| spellingShingle | Youwei Li Wei Wang Xiaoshuang Hou Wenda Huang Po Zhang Yue He Baofeng Wang Qiuhong Duan Feng Mao Dongsheng Guo Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth Cell Death and Disease |
| title | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth |
| title_full | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth |
| title_fullStr | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth |
| title_full_unstemmed | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth |
| title_short | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth |
| title_sort | glioma derived lrig3 interacts with neto2 in tumor associated macrophages to modulate microenvironment and suppress tumor growth |
| url | https://doi.org/10.1038/s41419-023-05555-z |
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