Targeting fibroblast-endothelial cell interactions in LAM pathogenesis using 3D spheroid models and spatial transcriptomics.

ABSTRACT: Lymphangioleiomyomatosis (LAM) is a progressive lung disease with limited treatments, largely because of an incomplete understanding of its pathogenesis. Lymphatic endothelial cells (LECs) invade LAM cell clusters, which include human melanoma black-45-positive epithelioid cells and smooth muscle α-actin-expressing LAM-associated fibroblasts (LAMFs). Recent evidence shows that LAMFs resemble cancer-associated fibroblasts, with LAMF-LEC interactions contributing to disease progression. To explore these mechanisms, we used spatial transcriptomics on LAM lung tissues and identified a gene cluster enriched in kinase signaling pathways linked to myofibroblasts and coexpressed with LEC markers. Kinase arrays revealed elevated PDGFR and FGFR in LAMFs. Using a 3D coculture spheroid model of primar

SUBMITTER: Koc-Gunel S 

PROVIDER: S-EPMC11949067 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature