Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer
Introduction: Causes of pain due to spinal metastases have been insufficiently investigated. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were the focus of this study. Both are known as proinflammatory cytokines associated with the pathophysiology of pain syndromes. It is well known that...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Japanese Society for Spine Surgery and Related Research
2019-07-01
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| Series: | Spine Surgery and Related Research |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/ssrr/3/3/3_2018-0106/_pdf/-char/en |
| _version_ | 1828842947037102080 |
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| author | Ai Mazaki Sumihisa Orita Kazuhide Inage Miyako Suzuki Kohki Abe Yasuhiro Shiga Masahiro Inoue Masaki Norimoto Tomotaka Umimura Seiji Ohtori Kazuyo Yamauchi |
| author_facet | Ai Mazaki Sumihisa Orita Kazuhide Inage Miyako Suzuki Kohki Abe Yasuhiro Shiga Masahiro Inoue Masaki Norimoto Tomotaka Umimura Seiji Ohtori Kazuyo Yamauchi |
| author_sort | Ai Mazaki |
| collection | DOAJ |
| description | Introduction: Causes of pain due to spinal metastases have been insufficiently investigated. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were the focus of this study. Both are known as proinflammatory cytokines associated with the pathophysiology of pain syndromes. It is well known that cancer cells produce these cytokines, but whether osteoclasts produce them as well remains unclear. We hypothesize that osteoclasts produce these cytokines; in other words, pain from spinal metastasis is stronger than pain from the primary tumor.
Methods: We made a rat spinal metastasis model of breast cancer (metastasis group) and models with a hole in the vertebrae (puncture group) and resected the vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to reconfirm that osteoclasts increase in vertebrae with spinal metastasis. We then evaluated TNF-α and IL-6 expression using immunohistochemistry and real-time polymerase chain reaction (PCR).
Results: The results of TRAP staining showed that osteoclasts increase in metastatic vertebrae. The osteoclasts in the puncture models were TNF-α negative but were TNF-α positive in the metastasis model. The osteoclasts in the puncture models and metastasis model were both IL-6 positive. According to the real-time PCR results, TNF-α in vertebrae increased in the metastasis model, but IL-6 did not increase in the metastasis model compared with in the puncture model.
Conclusions: The number of osteoclasts is higher in the metastasis model. While TNF in the osteoclasts increased in the spinal metastasis model, IL-6 did not. This probably means that breast cancer affects TNF production in osteoclasts. This increase of TNF-α may lead to pain from spinal metastasis. |
| first_indexed | 2024-12-12T20:35:25Z |
| format | Article |
| id | doaj.art-a97be0cb2e084bc3a6d7bfe4ab1053ae |
| institution | Directory Open Access Journal |
| issn | 2432-261X |
| language | English |
| last_indexed | 2024-12-12T20:35:25Z |
| publishDate | 2019-07-01 |
| publisher | The Japanese Society for Spine Surgery and Related Research |
| record_format | Article |
| series | Spine Surgery and Related Research |
| spelling | doaj.art-a97be0cb2e084bc3a6d7bfe4ab1053ae2022-12-22T00:12:55ZengThe Japanese Society for Spine Surgery and Related ResearchSpine Surgery and Related Research2432-261X2019-07-013326126610.22603/ssrr.2018-01062018-0106Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast CancerAi Mazaki0Sumihisa Orita1Kazuhide Inage2Miyako Suzuki3Kohki Abe4Yasuhiro Shiga5Masahiro Inoue6Masaki Norimoto7Tomotaka Umimura8Seiji Ohtori9Kazuyo Yamauchi10Department of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityDepartment of Orthopaedic Surgery, Graduate School of Medicine, The Chiba UniversityIntroduction: Causes of pain due to spinal metastases have been insufficiently investigated. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were the focus of this study. Both are known as proinflammatory cytokines associated with the pathophysiology of pain syndromes. It is well known that cancer cells produce these cytokines, but whether osteoclasts produce them as well remains unclear. We hypothesize that osteoclasts produce these cytokines; in other words, pain from spinal metastasis is stronger than pain from the primary tumor. Methods: We made a rat spinal metastasis model of breast cancer (metastasis group) and models with a hole in the vertebrae (puncture group) and resected the vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to reconfirm that osteoclasts increase in vertebrae with spinal metastasis. We then evaluated TNF-α and IL-6 expression using immunohistochemistry and real-time polymerase chain reaction (PCR). Results: The results of TRAP staining showed that osteoclasts increase in metastatic vertebrae. The osteoclasts in the puncture models were TNF-α negative but were TNF-α positive in the metastasis model. The osteoclasts in the puncture models and metastasis model were both IL-6 positive. According to the real-time PCR results, TNF-α in vertebrae increased in the metastasis model, but IL-6 did not increase in the metastasis model compared with in the puncture model. Conclusions: The number of osteoclasts is higher in the metastasis model. While TNF in the osteoclasts increased in the spinal metastasis model, IL-6 did not. This probably means that breast cancer affects TNF production in osteoclasts. This increase of TNF-α may lead to pain from spinal metastasis.https://www.jstage.jst.go.jp/article/ssrr/3/3/3_2018-0106/_pdf/-char/enosteoclasttnf-αil-6proinflammatory cytokinesspinal metastasisbreast cancerpain |
| spellingShingle | Ai Mazaki Sumihisa Orita Kazuhide Inage Miyako Suzuki Kohki Abe Yasuhiro Shiga Masahiro Inoue Masaki Norimoto Tomotaka Umimura Seiji Ohtori Kazuyo Yamauchi Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer Spine Surgery and Related Research osteoclast tnf-α il-6 proinflammatory cytokines spinal metastasis breast cancer pain |
| title | Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer |
| title_full | Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer |
| title_fullStr | Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer |
| title_full_unstemmed | Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer |
| title_short | Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer |
| title_sort | tumor necrosis factor α produced by osteoclasts might induce intractable pain in a rat spinal metastasis model of breast cancer |
| topic | osteoclast tnf-α il-6 proinflammatory cytokines spinal metastasis breast cancer pain |
| url | https://www.jstage.jst.go.jp/article/ssrr/3/3/3_2018-0106/_pdf/-char/en |
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