Interstitial pneumonia microenvironment promotes metastasis to the mediastinal lymph nodes and lungs

TL;DR

This study shows that the lung environment in interstitial pneumonia promotes lung cancer metastasis and suggests pirfenidone as a potential treatment.

Contribution

The study demonstrates that the interstitial pneumonia microenvironment enhances lung cancer metastasis and responds to pirfenidone treatment.

Findings

The IP lung environment promotes metastasis to mediastinal lymph nodes and contralateral lungs in a murine model.

Clinical data supports increased metastasis in ILD-associated lung cancer patients compared to those without ILD.

Pirfenidone treatment inhibited tumor progression in the IP lung cancer model.

Abstract

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.

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.

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.

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.

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