TGF-β signaling activated by cancer-associated fibroblasts determines the histological signature of lung adenocarcinoma

Invasive lung adenocarcinoma (LADC) is classified histologically as lepidic, acinar, papillary, micropapillary, or solid. We found that A549 human LADC cells formed tumors with distinct histological features—solid-type or acinar-type tumors—depending on the site of development in immunodeficient mice and that a solid-to-acinar transition (SAT) could be induced by cancer-associated fibroblasts (CAFs) in 3D cocultures with A549. To clarify the molecular mechanisms contributing to SAT induction, we performed RNA-seq analysis of four A549 tumor cell samples derived from solid- or acinar-type tumor tissue formed in vivo or from 3D tumor colonies formed in the presence or absence of CAFs in vitro. RNA-seq analysis of A549 cells isolated from solid-type or acinar-type tumors in immunodeficient mice by laser microdissection and A549 cells isolated from 3D cocultures in the presence or absence of CAFs by cell sorting.