Inhibition of autotaxin activity with IOA-289 decreases fibrosis in mouse E0771 breast tumors.

ABSTRACT: Tumor-associated fibrosis contributes to an immunosuppressive microenvironment that hinders effective anti-tumor immune responses. This study investigates the potential of IOA-289, a novel autotaxin (ATX) inhibitor, which blocks lysophosphatidate (LPA) production and signaling, in modulating fibrosis in breast tumors. Bioinformatic analysis of human breast tumors revealed a strong correlation between levels of LPA_1,-4 receptors and extracellular matrix (ECM) genes. Interaction of ECM molecules and integrin β1/CD44 between myofibroblasts and other cell types had the highest contribution to cell-cell communication. We showed that LPA induced α-smooth muscle actin mRNA in mouse mammary fibroblasts and increased expressions of collagen type-I α1 chain (COL1A1) and lamininγ1. IOA-289

SUBMITTER: Tang X 

PROVIDER: S-EPMC12280849 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature