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This study investigates the potential of IOA\u2010289, 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\n                    <jats:sub>1,\u20104<\/jats:sub>\n                    receptors and extracellular matrix (ECM) genes. Interaction of ECM molecules and integrin \u03b21\/CD44 between myofibroblasts and other cell types had the highest contribution to cell\u2013cell communication. We showed that LPA induced \u03b1\u2010smooth muscle actin mRNA in mouse mammary fibroblasts and increased expressions of collagen type\u2010I \u03b11 chain (\n                    <jats:italic>COL1A1<\/jats:italic>\n                    ) and laminin\u03b31. IOA\u2010289 decreased the expressions of\n                    <jats:italic>COL1A1<\/jats:italic>\n                    , fibronectin\u20101, and transforming growth factor \u03b21 (TGF\u03b21) in E0771 breast tumors in mice. Masson's trichrome staining revealed a marked decrease in collagen deposition within breast tumors of IOA\u2010289\u2010treated mice. Decreased tumor fibrosis aligns with previous findings that IOA\u2010289 enhanced the infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells and decreased fibrotic factors including leukemia inhibitory factor and transforming growth factor\u2010beta1 in tumors. We also demonstrated that E0771 cells express negligible ATX and LPA receptors. Therefore, ATX inhibition did not affect cancer cells directly in our model. These results underscore the potential of ATX inhibitors in reprogramming the tumor microenvironment to favor anti\u2010tumor immunity and attenuate fibrosis. ATX inhibitors are in clinical trials for treating idiopathic pulmonary fibrosis and pancreatic cancer. Our results support the development of ATX inhibitors as a strategy for improving the treatment of breast cancer and other diseases involving fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35471","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T21:35:53Z","timestamp":1746826553000},"page":"1205-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of autotaxin activity with\n                    <scp>IOA<\/scp>\n                    \u2010289 decreases fibrosis in mouse\n                    <scp>E0771<\/scp>\n                    breast tumors"],"prefix":"10.1002","volume":"157","author":[{"given":"Xiaoyun","family":"Tang","sequence":"first","affiliation":[{"name":"Cancer Research Institute of Northern Alberta  Edmonton Alberta Canada"},{"name":"Department of Biochemistry University of Alberta  Edmonton Alberta 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