Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination
Abstract While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival fu...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42303-5 |
| _version_ | 1797558287892217856 |
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| author | Chih-Wei Chou Chia-Nung Hung Cheryl Hsiang-Ling Chiu Xi Tan Meizhen Chen Chien-Chin Chen Moawiz Saeed Che-Wei Hsu Michael A. Liss Chiou-Miin Wang Zhao Lai Nathaniel Alvarez Pawel A. Osmulski Maria E. Gaczynska Li-Ling Lin Veronica Ortega Nameer B. Kirma Kexin Xu Zhijie Liu Addanki P. Kumar Josephine A. Taverna Gopalrao V. N. Velagaleti Chun-Liang Chen Zhao Zhang Tim Hui-Ming Huang |
| author_facet | Chih-Wei Chou Chia-Nung Hung Cheryl Hsiang-Ling Chiu Xi Tan Meizhen Chen Chien-Chin Chen Moawiz Saeed Che-Wei Hsu Michael A. Liss Chiou-Miin Wang Zhao Lai Nathaniel Alvarez Pawel A. Osmulski Maria E. Gaczynska Li-Ling Lin Veronica Ortega Nameer B. Kirma Kexin Xu Zhijie Liu Addanki P. Kumar Josephine A. Taverna Gopalrao V. N. Velagaleti Chun-Liang Chen Zhao Zhang Tim Hui-Ming Huang |
| author_sort | Chih-Wei Chou |
| collection | DOAJ |
| description | Abstract While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease. |
| first_indexed | 2024-03-10T17:28:08Z |
| format | Article |
| id | doaj.art-2948fd02380348cca98fb04b6c8cbabb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:28:08Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-2948fd02380348cca98fb04b6c8cbabb2023-11-20T10:05:51ZengNature PortfolioNature Communications2041-17232023-10-0114112010.1038/s41467-023-42303-5Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant disseminationChih-Wei Chou0Chia-Nung Hung1Cheryl Hsiang-Ling Chiu2Xi Tan3Meizhen Chen4Chien-Chin Chen5Moawiz Saeed6Che-Wei Hsu7Michael A. Liss8Chiou-Miin Wang9Zhao Lai10Nathaniel Alvarez11Pawel A. Osmulski12Maria E. Gaczynska13Li-Ling Lin14Veronica Ortega15Nameer B. Kirma16Kexin Xu17Zhijie Liu18Addanki P. Kumar19Josephine A. Taverna20Gopalrao V. N. Velagaleti21Chun-Liang Chen22Zhao Zhang23Tim Hui-Ming Huang24Department of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Pathology, Ditmanson Medical Foundation Chia-Yi Christian HospitalDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Urology, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Pathology and Laboratory Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Pathology and Laboratory Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterDepartment of Molecular Medicine, University of Texas Health Science CenterAbstract While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.https://doi.org/10.1038/s41467-023-42303-5 |
| spellingShingle | Chih-Wei Chou Chia-Nung Hung Cheryl Hsiang-Ling Chiu Xi Tan Meizhen Chen Chien-Chin Chen Moawiz Saeed Che-Wei Hsu Michael A. Liss Chiou-Miin Wang Zhao Lai Nathaniel Alvarez Pawel A. Osmulski Maria E. Gaczynska Li-Ling Lin Veronica Ortega Nameer B. Kirma Kexin Xu Zhijie Liu Addanki P. Kumar Josephine A. Taverna Gopalrao V. N. Velagaleti Chun-Liang Chen Zhao Zhang Tim Hui-Ming Huang Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination Nature Communications |
| title | Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination |
| title_full | Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination |
| title_fullStr | Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination |
| title_full_unstemmed | Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination |
| title_short | Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination |
| title_sort | phagocytosis initiated tumor hybrid cells acquire a c myc mediated quasi polarization state for immunoevasion and distant dissemination |
| url | https://doi.org/10.1038/s41467-023-42303-5 |
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