Dynamic change of polarity is involved in the establishment of metastasis by Spread Through Air Spaces

ABSTRACT: Spread through the airspace (STAS) is a histological finding of lung tumors where tumor cells exist within the airspace of the lung parenchyma beyond the margin of the main tumor. Although STAS is an important prognostic factor, the etiology of STAS is largely unknown. In this study, histopathological analysis revealed the presence of an apical membrane outside the STAS surrounding colorectal cancer (CRC) lung metastases and lung adenocarcinomas. When CRC cells were intratracheally administered to mice, cancer cell clusters had greater metastatic potential than single cells. An in vitro model of STAS co-cultured with CRC organoids and 2D cultured mouse airway epithelial organoids (2D-MAO) was established. Adhesion of CRC clusters to 2D-MAO was much less than to type I collagen or endothelial cells, suggesting a protective role of the airway epithelium against adhesion of cancer cell clusters. Loss of the apical membrane of CRC clusters at the contact surface with 2D-MAO after adhesion was responsible for establishing adhesion. In the co-culture model, airway epithelium stimulated by TGF-β1 promoted adhesion of CRC organoids to the airway epithelium. Among TGF-β1-induced genes in airway epithelium, FSTL1 promoted CRC organoid adhesion, suggesting that FSTL1 may promote metastasis by STAS in the inflammatory microenvironment. Elucidating the mechanism of STAS will contribute to the development of therapies to prevent STAS and its associated metastases. To examine the downstream of TGF-β1 in 2D-MAO, gene expression profiles were analyzed and compared between TGF-β1-treated with non-treated 2D-MAO. The number of differentially expressed genes that showed statistically more than 2-fold or greater changes was 709, with 571 upregulated and 138 downregulated.

ORGANISM(S): Mus musculus

PROVIDER: GSE255842 | GEO | 2024/03/01

REPOSITORIES: GEO