Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression
Abstract Background The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04756-6 |
| _version_ | 1797414194539134976 |
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| author | Kiyofumi Shimoji Taku Nakashima Takeshi Masuda Masashi Namba Shinjiro Sakamoto Kakuhiro Yamaguchi Yasushi Horimasu Takahiro Mimae Shintaro Miyamoto Hiroshi Iwamoto Kazunori Fujitaka Hironobu Hamada Morihito Okada Noboru Hattori |
| author_facet | Kiyofumi Shimoji Taku Nakashima Takeshi Masuda Masashi Namba Shinjiro Sakamoto Kakuhiro Yamaguchi Yasushi Horimasu Takahiro Mimae Shintaro Miyamoto Hiroshi Iwamoto Kazunori Fujitaka Hironobu Hamada Morihito Okada Noboru Hattori |
| author_sort | Kiyofumi Shimoji |
| collection | DOAJ |
| description | Abstract Background The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents. Methods A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings. Results In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis. Conclusions The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression. |
| first_indexed | 2024-03-09T05:29:33Z |
| format | Article |
| id | doaj.art-adb9342598e843a3a3a376c7407dd241 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-09T05:29:33Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-adb9342598e843a3a3a376c7407dd2412023-12-03T12:34:21ZengBMCJournal of Translational Medicine1479-58762023-11-0121111910.1186/s12967-023-04756-6Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progressionKiyofumi Shimoji0Taku Nakashima1Takeshi Masuda2Masashi Namba3Shinjiro Sakamoto4Kakuhiro Yamaguchi5Yasushi Horimasu6Takahiro Mimae7Shintaro Miyamoto8Hiroshi Iwamoto9Kazunori Fujitaka10Hironobu Hamada11Morihito Okada12Noboru Hattori13Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityAbstract Background The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents. Methods A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings. Results In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis. Conclusions The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression.https://doi.org/10.1186/s12967-023-04756-6Interstitial pneumoniaLung cancerHypoxia-inducible factorAlpha subunitTumor microenvironmentAscorbic acid |
| spellingShingle | Kiyofumi Shimoji Taku Nakashima Takeshi Masuda Masashi Namba Shinjiro Sakamoto Kakuhiro Yamaguchi Yasushi Horimasu Takahiro Mimae Shintaro Miyamoto Hiroshi Iwamoto Kazunori Fujitaka Hironobu Hamada Morihito Okada Noboru Hattori Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression Journal of Translational Medicine Interstitial pneumonia Lung cancer Hypoxia-inducible factor Alpha subunit Tumor microenvironment Ascorbic acid |
| title | Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression |
| title_full | Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression |
| title_fullStr | Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression |
| title_full_unstemmed | Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression |
| title_short | Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression |
| title_sort | hypoxia inducible factor 1α modulates interstitial pneumonia mediated lung cancer progression |
| topic | Interstitial pneumonia Lung cancer Hypoxia-inducible factor Alpha subunit Tumor microenvironment Ascorbic acid |
| url | https://doi.org/10.1186/s12967-023-04756-6 |
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