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Sphingomyelin synthase 2 (SMS2) is involved in inflammatory diseases such as obesity and diabetes mellitus by regulation of the SM\/ceramide balance. However, the involvement of SMS2 in TME formation and metastasis is largely unknown. Here, we report that SMS2\u2010deficient (SMS2\u2010KO) mice show suppressed the EL4 cell infiltration to liver and prolonged survival time. ICAM\u20101 was identified as a candidate for the inhibition of TME formation in immortalized mouse embryonic fibroblasts (tMEFs) from mRNA array analysis for CAMs. Reduced SM\/ceramide balance in SMS2\u2010KO tMEFs suppressed the attachment of EL4 cells through transcriptional reduction of ICAM\u20101 by the inhibition of NF\u2010\u03baB activation. TNF\u2010\u03b1\u2010induced NF\u2010\u03baB activation and subsequent induction of ICAM\u20101 were suppressed in SMS2\u2010KO tMEFs but restored by SMS2 re\u2010introduction. In the EL4 cell infiltration mouse model, EL4 injection increased ICAM\u20101 expression in WT liver but not in SMS2\u2010KO mouse liver. Therefore, inhibition of SMS2 may be a therapeutic target to suppress the infiltration of malignant lymphoma.<\/jats:p>","DOI":"10.1096\/fj.201901783rr","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:16:13Z","timestamp":1579738573000},"page":"3838-3854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Deficiency of sphingomyelin synthase 2 prolongs survival by the inhibition of lymphoma infiltration through ICAM\u20101 reduction"],"prefix":"10.1096","volume":"34","author":[{"given":"Makoto","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Department of Life Science Medical Research Institute, Kanazawa Medical University Kahoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshibumi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Hematology and Immunology Kanazawa Medical University 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