Computed tomography reveals microenvironment changes in premetastatic lung.

Abstract

Microenvironment changes had occurred in the metastatic organs before the arriving of the metastatic tumor cells. In this study, we evaluated the effectiveness of computed tomography (CT) images in quantifying the microenvironment changes in the premetastatic lung under both laboratory and clinical conditions. Free-breathing Balb/c mice underwent micro-CT repeatedly after the implantation of 4T1 breast tumor. CT-derived indicators (aerated lung volume, lung tissue volume, total lung volume, mean lung density, and the ratio of aerated lung volume to the total lung volume) were quantified. Hematoxylin-eosin staining was used to display the microenvironment changes in premetastatic lung. Moreover, we examined healthy adult women, adult women with histopathologically confirmed primary breast cancer, and adult women with histopathologically confirmed primary breast cancer and lung metastases in our institution to test whether the indicators derived from lung CT images changed with the growth of breast cancer. In 4T1 tumor-bearing mice, lung density is increased before lung masses can be recognized on CT images and is correlated with the severity of inflammation in the lung microenvironment. In primary breast tumor-bearing patients, lung density is also increased before the clinical diagnosis of pulmonary metastasis and is correlated with disease score, which represents tumor progression. CT is a reliable and quantitative tool that yields dynamic information on metastatic processes. Microenvironmental changes had occurred in patients' lung tissue before the clinical diagnosis of pulmonary metastasis. Our research will provide new insight for clinical research on the premetastatic niche. • CT, which provides dynamic information on metastatic processes, is a reliable and quantitative tool to bridge laboratory and clinical studies of the premetastatic niche. • We confirmed that microenvironmental changes occurred in patients' lung tissue before clinicians could diagnose pulmonary metastasis. • Our results provide evidence for the study of the premetastatic niche by analyzing information obtained from CT images.