A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production
Osteosarcoma, a common aggressive and malignant cancer, appears in the musculoskeletal system among young adults. The major cause of mortality in osteosarcoma was the recurrence of lung metastases. However, the molecular mechanisms of metastasis involved in osteosarcomas remain unclear. Recently, CX...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.735277/full |
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| author | Chiang-Wen Lee Chiang-Wen Lee Chiang-Wen Lee Yao-Chang Chiang Yao-Chang Chiang Yao-Chang Chiang Pei-An Yu Pei-An Yu Kuo-Ti Peng Kuo-Ti Peng Miao-Ching Chi Miao-Ching Chi Miao-Ching Chi Ming-Hsueh Lee Ming-Hsueh Lee Mei-Ling Fang Mei-Ling Fang Kuan-Han Lee Lee-Fen Hsu Lee-Fen Hsu Ju-Fang Liu Ju-Fang Liu |
| author_facet | Chiang-Wen Lee Chiang-Wen Lee Chiang-Wen Lee Yao-Chang Chiang Yao-Chang Chiang Yao-Chang Chiang Pei-An Yu Pei-An Yu Kuo-Ti Peng Kuo-Ti Peng Miao-Ching Chi Miao-Ching Chi Miao-Ching Chi Ming-Hsueh Lee Ming-Hsueh Lee Mei-Ling Fang Mei-Ling Fang Kuan-Han Lee Lee-Fen Hsu Lee-Fen Hsu Ju-Fang Liu Ju-Fang Liu |
| author_sort | Chiang-Wen Lee |
| collection | DOAJ |
| description | Osteosarcoma, a common aggressive and malignant cancer, appears in the musculoskeletal system among young adults. The major cause of mortality in osteosarcoma was the recurrence of lung metastases. However, the molecular mechanisms of metastasis involved in osteosarcomas remain unclear. Recently, CXCL1 and CXCR2 have been crucial indicators for lung metastasis in osteosarcoma by paracrine releases, suggesting the involvement of directing neutrophils into tumor microenvironment. In this study, overexpression of CXCL1 has a positive correlation with the migratory and invasive activities in osteosarcoma cell lines. Furthermore, the signaling pathway, CXCR2/FAK/PI3K/Akt, is activated through CXCL1 by promoting vascular cell adhesion molecule 1 (VCAM-1) via upregulation of nuclear factor-kappa B (NF-κB) expression and nuclear translocation. The in vivo animal model further demonstrated that CXCL1 serves as a critical promoter in osteosarcoma metastasis to the lung. The correlated expression of CXCL1 and VCAM-1 was observed in the immunohistochemistry staining from human osteosarcoma specimens. Our findings demonstrate the cascade mechanism regulating the network in lung metastasis osteosarcoma, therefore indicating that the CXCL1/CXCR2 pathway is a worthwhile candidate to further develop treatment schemas. |
| first_indexed | 2024-12-21T05:37:39Z |
| format | Article |
| id | doaj.art-296390ee2ef34efebbd9c9d5c03c6791 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T05:37:39Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-296390ee2ef34efebbd9c9d5c03c67912022-12-21T19:14:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.735277735277A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 ProductionChiang-Wen Lee0Chiang-Wen Lee1Chiang-Wen Lee2Yao-Chang Chiang3Yao-Chang Chiang4Yao-Chang Chiang5Pei-An Yu6Pei-An Yu7Kuo-Ti Peng8Kuo-Ti Peng9Miao-Ching Chi10Miao-Ching Chi11Miao-Ching Chi12Ming-Hsueh Lee13Ming-Hsueh Lee14Mei-Ling Fang15Mei-Ling Fang16Kuan-Han Lee17Lee-Fen Hsu18Lee-Fen Hsu19Ju-Fang Liu20Ju-Fang Liu21Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi, TaiwanDepartment of Nursing, Chang Gung University of Science and Technology, Puzi, TaiwanDivision of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi, TaiwanDepartment of Nursing, Chang Gung University of Science and Technology, Puzi, TaiwanDivision of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi, TaiwanSports Medicine Center, Chang Gung Memorial Hospital at Chia Yi, Chiayi, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi, TaiwanCollege of Medicine, Chang Gung University, Taoyuan, TaiwanDivision of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi, TaiwanDepartment of Respiratory Care, Chang Gung University of Science and Technology, Puzi, TaiwanDivision of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Kaohsiung, TaiwanDepartment of Respiratory Care, Chang Gung University of Science and Technology, Puzi, TaiwanDivision of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, TaiwanCenter for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, Taiwan0Super Micro Research and Technology Center, Cheng Shiu University, Kaohsiung, Taiwan1Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, TaiwanDepartment of Respiratory Care, Chang Gung University of Science and Technology, Puzi, TaiwanDivision of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan2School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan3Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, TaiwanOsteosarcoma, a common aggressive and malignant cancer, appears in the musculoskeletal system among young adults. The major cause of mortality in osteosarcoma was the recurrence of lung metastases. However, the molecular mechanisms of metastasis involved in osteosarcomas remain unclear. Recently, CXCL1 and CXCR2 have been crucial indicators for lung metastasis in osteosarcoma by paracrine releases, suggesting the involvement of directing neutrophils into tumor microenvironment. In this study, overexpression of CXCL1 has a positive correlation with the migratory and invasive activities in osteosarcoma cell lines. Furthermore, the signaling pathway, CXCR2/FAK/PI3K/Akt, is activated through CXCL1 by promoting vascular cell adhesion molecule 1 (VCAM-1) via upregulation of nuclear factor-kappa B (NF-κB) expression and nuclear translocation. The in vivo animal model further demonstrated that CXCL1 serves as a critical promoter in osteosarcoma metastasis to the lung. The correlated expression of CXCL1 and VCAM-1 was observed in the immunohistochemistry staining from human osteosarcoma specimens. Our findings demonstrate the cascade mechanism regulating the network in lung metastasis osteosarcoma, therefore indicating that the CXCL1/CXCR2 pathway is a worthwhile candidate to further develop treatment schemas.https://www.frontiersin.org/articles/10.3389/fonc.2021.735277/fullosteosarcomametastasisCXCL1VCAM-1migration |
| spellingShingle | Chiang-Wen Lee Chiang-Wen Lee Chiang-Wen Lee Yao-Chang Chiang Yao-Chang Chiang Yao-Chang Chiang Pei-An Yu Pei-An Yu Kuo-Ti Peng Kuo-Ti Peng Miao-Ching Chi Miao-Ching Chi Miao-Ching Chi Ming-Hsueh Lee Ming-Hsueh Lee Mei-Ling Fang Mei-Ling Fang Kuan-Han Lee Lee-Fen Hsu Lee-Fen Hsu Ju-Fang Liu Ju-Fang Liu A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production Frontiers in Oncology osteosarcoma metastasis CXCL1 VCAM-1 migration |
| title | A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production |
| title_full | A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production |
| title_fullStr | A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production |
| title_full_unstemmed | A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production |
| title_short | A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production |
| title_sort | role of cxcl1 drives osteosarcoma lung metastasis via vcam 1 production |
| topic | osteosarcoma metastasis CXCL1 VCAM-1 migration |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.735277/full |
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