| First Author | Taniguchi M | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 3 | Pages | 3838-3854 |
| PubMed ID | 31970839 | Mgi Jnum | J:303789 |
| Mgi Id | MGI:6512619 | Doi | 10.1096/fj.201901783RR |
| Citation | Taniguchi M, et al. (2020) Deficiency of sphingomyelin synthase 2 prolongs survival by the inhibition of lymphoma infiltration through ICAM-1 reduction. FASEB J 34(3):3838-3854 |
| abstractText | The tumor microenvironment (TME) formation involving host cells and cancer cells through cell adhesion molecules (CAMs) is essential for the multiple steps of cancer metastasis and growth. 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-deficient (SMS2-KO) mice show suppressed the EL4 cell infiltration to liver and prolonged survival time. ICAM-1 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-KO tMEFs suppressed the attachment of EL4 cells through transcriptional reduction of ICAM-1 by the inhibition of NF-kappaB activation. TNF-alpha-induced NF-kappaB activation and subsequent induction of ICAM-1 were suppressed in SMS2-KO tMEFs but restored by SMS2 re-introduction. In the EL4 cell infiltration mouse model, EL4 injection increased ICAM-1 expression in WT liver but not in SMS2-KO mouse liver. Therefore, inhibition of SMS2 may be a therapeutic target to suppress the infiltration of malignant lymphoma. |
