ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1657948
This article is part of the Research TopicTargeting cancer-associated fibroblasts: Disrupting immune evasion and therapy resistanceView all 8 articles
Interstitial pneumonia microenvironment promotes metastasis to the mediastinal lymph nodes and lungs
Provisionally accepted
- Miyazaki Daigaku - Kiyotake Campus, Miyazaki, Japan
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Introduction: The prognosis of patients with lung cancer and interstitial lung disease (ILD) is worse than that of patients without ILDs; however, therapeutic options for ILD-associated lung cancer are severely limited. Although ILD is associated with an increased incidence of lung cancer, it is unclear whether the ILD lung environment affects the biological behavior of lung cancer. Methods: We tested our hypothesis that the lung environment of ILD is associated with the biological behavior and progression of lung cancer using an in vivo murine model of interstitial pneumonia (IP) and lung cancer. Results: The bleomycin-induced IP lung environment promoted metastasis to the mediastinal lymph nodes or contralateral lungs in an orthotopic model of lung cancer. The results of our in vivo experiments were supported by clinical data, which indicated that a significantly greater number of carcinomas with vascular invasion and lymphatic permeation, lymph node metastases, and intrapulmonary metastases were found in patients with clinical stage I non-small cell lung cancer and ILD than in those without ILD. In addition, pharmacological treatment of the IP lung environment with pirfenidone (PFD) inhibited tumor progression in the IP lung cancer model. Conclusion: We found that the IP lung environment promotes lung cancer metastasis. The results of this study may pave the way for further clinical studies on the use of PFD alone or in conjunction with conventional chemotherapy in patients with lung cancer and ILD.
Keywords: lung cancer, Interstitial Lung Disease, fibroblast, metastasis, Pirfenidone
Received: 05 Aug 2025; Accepted: 26 Sep 2025.
Copyright: © 2025 Maeda, Inomata and Yamada. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ryo Maeda, ryo_maeda@med.miyazaki-u.ac.jp
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