Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer
Abstract Tumor-derived exosomes participate in omental metastatic colonization of ovarian cancer by inducing an adaptive response in the tumor microenvironment. However, cell–cell communication via exosomes between primary tumor cells and the microenvironment of distant omentum and the mechanism of...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05472-7 |
| _version_ | 1811302162978832384 |
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| author | Haiyang Li Cheng Zeng Chang Shu Yuanyuan Cao Wengui Shao Mengjie Zhang Hongyong Cao Shuli Zhao |
| author_facet | Haiyang Li Cheng Zeng Chang Shu Yuanyuan Cao Wengui Shao Mengjie Zhang Hongyong Cao Shuli Zhao |
| author_sort | Haiyang Li |
| collection | DOAJ |
| description | Abstract Tumor-derived exosomes participate in omental metastatic colonization of ovarian cancer by inducing an adaptive response in the tumor microenvironment. However, cell–cell communication via exosomes between primary tumor cells and the microenvironment of distant omentum and the mechanism of pre-metastatic niche formation are poorly understood. Here, we demonstrated that ETS1-overexpressing ovarian cancer cells secreted larger exosomes with higher laminin levels. In addition, ovarian cancer exosomes could be taken up by omental macrophages through integrin and laminin interaction. Compared with control exosomes, exosomes derived from ETS1-overexpressing ovarian cancer cells (LV-ETS1 Exos) stimulated the polarization of more macrophages toward the M2 phenotype (CD163 marker), as well as the production of more CXCL5 and CCL2 in macrophages, via integrin αvβ5/AKT/Sp1 signaling. In vivo experiments showed that LV-ETS1 Exos promoted omental metastasis of ovarian cancer by mediating the tumor-promoting effect of macrophages, which could be neutralized by integrin ανβ5 inhibitor cilengitide. These results indicated that ETS1 could drive ovarian cancer cells to release exosomes with higher laminin levels, thereby accelerating the exosome-mediated pro-metastatic effects of omental macrophages via the integrin αvβ5/AKT/Sp1 signaling pathway, and the integrin ανβ5 inhibitor cilengitide could inhibit omental metastasis of ovarian cancer driven by tumor-derived exosomes. |
| first_indexed | 2024-04-13T07:23:08Z |
| format | Article |
| id | doaj.art-0a39fa9c42d24531bab3a657a0901508 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T07:23:08Z |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-0a39fa9c42d24531bab3a657a09015082022-12-22T02:56:33ZengNature Publishing GroupCell Death and Disease2041-48892022-12-01131211510.1038/s41419-022-05472-7Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancerHaiyang Li0Cheng Zeng1Chang Shu2Yuanyuan Cao3Wengui Shao4Mengjie Zhang5Hongyong Cao6Shuli Zhao7Department of General Surgery, Nanjing First Hospital, Nanjing Medical UniversityGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical UniversityGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical UniversityGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical UniversityGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical UniversityGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical UniversityDepartment of General Surgery, Nanjing First Hospital, Nanjing Medical UniversityGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical UniversityAbstract Tumor-derived exosomes participate in omental metastatic colonization of ovarian cancer by inducing an adaptive response in the tumor microenvironment. However, cell–cell communication via exosomes between primary tumor cells and the microenvironment of distant omentum and the mechanism of pre-metastatic niche formation are poorly understood. Here, we demonstrated that ETS1-overexpressing ovarian cancer cells secreted larger exosomes with higher laminin levels. In addition, ovarian cancer exosomes could be taken up by omental macrophages through integrin and laminin interaction. Compared with control exosomes, exosomes derived from ETS1-overexpressing ovarian cancer cells (LV-ETS1 Exos) stimulated the polarization of more macrophages toward the M2 phenotype (CD163 marker), as well as the production of more CXCL5 and CCL2 in macrophages, via integrin αvβ5/AKT/Sp1 signaling. In vivo experiments showed that LV-ETS1 Exos promoted omental metastasis of ovarian cancer by mediating the tumor-promoting effect of macrophages, which could be neutralized by integrin ανβ5 inhibitor cilengitide. These results indicated that ETS1 could drive ovarian cancer cells to release exosomes with higher laminin levels, thereby accelerating the exosome-mediated pro-metastatic effects of omental macrophages via the integrin αvβ5/AKT/Sp1 signaling pathway, and the integrin ανβ5 inhibitor cilengitide could inhibit omental metastasis of ovarian cancer driven by tumor-derived exosomes.https://doi.org/10.1038/s41419-022-05472-7 |
| spellingShingle | Haiyang Li Cheng Zeng Chang Shu Yuanyuan Cao Wengui Shao Mengjie Zhang Hongyong Cao Shuli Zhao Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer Cell Death and Disease |
| title | Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer |
| title_full | Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer |
| title_fullStr | Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer |
| title_full_unstemmed | Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer |
| title_short | Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer |
| title_sort | laminins in tumor derived exosomes upregulated by ets1 reprogram omental macrophages to promote omental metastasis of ovarian cancer |
| url | https://doi.org/10.1038/s41419-022-05472-7 |
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