Deficiency of sphingomyelin synthase 2 prolongs survival by the inhibition of lymphoma infiltration through ICAM-1 reduction.


Journal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484

Informations de publication

Date de publication:
03 2020
Historique:
received: 16 07 2019
revised: 10 12 2019
accepted: 23 12 2019
pubmed: 24 1 2020
medline: 26 1 2021
entrez: 24 1 2020
Statut: ppublish

Résumé

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-κB activation. TNF-α-induced NF-κB 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.

Identifiants

pubmed: 31970839
doi: 10.1096/fj.201901783RR
doi:

Substances chimiques

Icam1 protein, mouse 0
RNA, Messenger 0
Tumor Necrosis Factor-alpha 0
Intercellular Adhesion Molecule-1 126547-89-5
Glucosyltransferases EC 2.4.1.-
ceramide glucosyltransferase EC 2.4.1.80
Transferases (Other Substituted Phosphate Groups) EC 2.7.8.-
Sgms2 protein, mouse EC 2.7.8.27

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3838-3854

Informations de copyright

© 2020 Federation of American Societies for Experimental Biology.

Références

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Auteurs

Makoto Taniguchi (M)

Department of Life Science, Medical Research Institute, Kanazawa Medical University, Kahoku, Japan.

Yoshibumi Ueda (Y)

Faculty of Medicine, Department of Hematology and Immunology, Kanazawa Medical University, Kahoku, Japan.
Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.

Michiko Matsushita (M)

Department of Pathobiological Science and Technology, School of Health Science, University of Tottori, Tottori, Japan.

Shingo Nagaya (S)

Faculty of Medicine, Department of Hematology and Immunology, Kanazawa Medical University, Kahoku, Japan.

Chieko Hashizume (C)

Faculty of Medicine, Department of Hematology and Immunology, Kanazawa Medical University, Kahoku, Japan.

Kenta Arai (K)

Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.

Kazuya Kabayama (K)

Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.
Project Research Center, Graduate School of Science, Osaka University, Osaka, Japan.

Koichi Fukase (K)

Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.
Project Research Center, Graduate School of Science, Osaka University, Osaka, Japan.

Ken Watanabe (K)

Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Japan.

Lusi Oka Wardhani (LO)

Division of Molecular Pathology, Faculty of Medicine, Department of Microbiology and Pathology, Tottori University, Tottori, Japan.

Kazuhiko Hayashi (K)

Division of Molecular Pathology, Faculty of Medicine, Department of Microbiology and Pathology, Tottori University, Tottori, Japan.

Toshiro Okazaki (T)

Faculty of Medicine, Department of Hematology and Immunology, Kanazawa Medical University, Kahoku, Japan.
Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku, Japan.

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