The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice
Abstract Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued at 70%. Thus, development of new treatment app...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49016-1 |
| _version_ | 1797398112345522176 |
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| author | Naoto Yoshimura Ryusho Kariya Masaki Shimada Makoto Tateyama Hideto Matsunaga Yuto Shibata Shuntaro Tanimura Kosei Takata Takahiro Arima Junki Kawakami Kazuya Maeda Yuko Fukuma Masaru Uragami Katsumasa Ideo Kazuki Sugimoto Ryuji Yonemitsu Kozo Matsushita Satoshi Hisanaga Masaki Yugami Yusuke Uehara Tetsuro Masuda Takayuki Nakamura Takuya Tokunaga Tatsuki Karasugi Takanao Sueyoshi Hiro Sato Yoichiro Iwakura Kimi Araki Eisuke Kobayashi Seiji Okada Takeshi Miyamoto |
| author_facet | Naoto Yoshimura Ryusho Kariya Masaki Shimada Makoto Tateyama Hideto Matsunaga Yuto Shibata Shuntaro Tanimura Kosei Takata Takahiro Arima Junki Kawakami Kazuya Maeda Yuko Fukuma Masaru Uragami Katsumasa Ideo Kazuki Sugimoto Ryuji Yonemitsu Kozo Matsushita Satoshi Hisanaga Masaki Yugami Yusuke Uehara Tetsuro Masuda Takayuki Nakamura Takuya Tokunaga Tatsuki Karasugi Takanao Sueyoshi Hiro Sato Yoichiro Iwakura Kimi Araki Eisuke Kobayashi Seiji Okada Takeshi Miyamoto |
| author_sort | Naoto Yoshimura |
| collection | DOAJ |
| description | Abstract Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued at 70%. Thus, development of new treatment approaches is needed. Here, we report that IL-17, a proinflammatory cytokine, increases osteosarcoma mortality in a mouse model with AX osteosarcoma cells. AX cell transplantation into wild-type mice resulted in 100% mortality due to ectopic ossification and multi-organ metastasis. However, AX cell transplantation into IL-17-deficient mice significantly prolonged survival relative to controls. CD4-positive cells adjacent to osteosarcoma cells express IL-17, while osteosarcoma cells express the IL-17 receptor IL-17RA. Although AX cells can undergo osteoblast differentiation, as can patient osteosarcoma cells, IL-17 significantly inhibited that differentiation, indicating that IL-17 maintains AX cells in the undifferentiated state seen in malignant tumors. By contrast, IL-17RA-deficient mice transplanted with AX cells showed survival comparable to wild-type mice transplanted with AX cells. Biopsy specimens collected from osteosarcoma patients showed higher expression of IL-17RA compared to IL-17. These findings suggest that IL-17 is essential to maintain osteosarcoma cells in an undifferentiated state and could be a therapeutic target for suppressing tumorigenesis. |
| first_indexed | 2024-03-09T01:20:02Z |
| format | Article |
| id | doaj.art-ed559e9c0ee0472ab0240adfebdfaea7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:20:02Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ed559e9c0ee0472ab0240adfebdfaea72023-12-10T12:14:13ZengNature PortfolioScientific Reports2045-23222023-12-0113111310.1038/s41598-023-49016-1The IL-17-IL-17RA axis is required to promote osteosarcoma progression in miceNaoto Yoshimura0Ryusho Kariya1Masaki Shimada2Makoto Tateyama3Hideto Matsunaga4Yuto Shibata5Shuntaro Tanimura6Kosei Takata7Takahiro Arima8Junki Kawakami9Kazuya Maeda10Yuko Fukuma11Masaru Uragami12Katsumasa Ideo13Kazuki Sugimoto14Ryuji Yonemitsu15Kozo Matsushita16Satoshi Hisanaga17Masaki Yugami18Yusuke Uehara19Tetsuro Masuda20Takayuki Nakamura21Takuya Tokunaga22Tatsuki Karasugi23Takanao Sueyoshi24Hiro Sato25Yoichiro Iwakura26Kimi Araki27Eisuke Kobayashi28Seiji Okada29Takeshi Miyamoto30Department of Orthopedic Surgery, Kumamoto UniversityLaboratory of Molecular Cell Biology, School of Pharmaceutical Sciences, Kobe Gakuin UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityDivision of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of ScienceDivision of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto UniversityDivision of Musculoskeletal Oncology, National Cancer Center HospitalDivision of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto UniversityDepartment of Orthopedic Surgery, Kumamoto UniversityAbstract Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued at 70%. Thus, development of new treatment approaches is needed. Here, we report that IL-17, a proinflammatory cytokine, increases osteosarcoma mortality in a mouse model with AX osteosarcoma cells. AX cell transplantation into wild-type mice resulted in 100% mortality due to ectopic ossification and multi-organ metastasis. However, AX cell transplantation into IL-17-deficient mice significantly prolonged survival relative to controls. CD4-positive cells adjacent to osteosarcoma cells express IL-17, while osteosarcoma cells express the IL-17 receptor IL-17RA. Although AX cells can undergo osteoblast differentiation, as can patient osteosarcoma cells, IL-17 significantly inhibited that differentiation, indicating that IL-17 maintains AX cells in the undifferentiated state seen in malignant tumors. By contrast, IL-17RA-deficient mice transplanted with AX cells showed survival comparable to wild-type mice transplanted with AX cells. Biopsy specimens collected from osteosarcoma patients showed higher expression of IL-17RA compared to IL-17. These findings suggest that IL-17 is essential to maintain osteosarcoma cells in an undifferentiated state and could be a therapeutic target for suppressing tumorigenesis.https://doi.org/10.1038/s41598-023-49016-1 |
| spellingShingle | Naoto Yoshimura Ryusho Kariya Masaki Shimada Makoto Tateyama Hideto Matsunaga Yuto Shibata Shuntaro Tanimura Kosei Takata Takahiro Arima Junki Kawakami Kazuya Maeda Yuko Fukuma Masaru Uragami Katsumasa Ideo Kazuki Sugimoto Ryuji Yonemitsu Kozo Matsushita Satoshi Hisanaga Masaki Yugami Yusuke Uehara Tetsuro Masuda Takayuki Nakamura Takuya Tokunaga Tatsuki Karasugi Takanao Sueyoshi Hiro Sato Yoichiro Iwakura Kimi Araki Eisuke Kobayashi Seiji Okada Takeshi Miyamoto The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice Scientific Reports |
| title | The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice |
| title_full | The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice |
| title_fullStr | The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice |
| title_full_unstemmed | The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice |
| title_short | The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice |
| title_sort | il 17 il 17ra axis is required to promote osteosarcoma progression in mice |
| url | https://doi.org/10.1038/s41598-023-49016-1 |
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