期刊
COMMUNICATIONS BIOLOGY
卷 3, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s42003-020-01333-1
关键词
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资金
- Italian Ministry of Education, University and Research (MIUR) program Departments of Excellence 2018-2022
- FOHN Project
- AGING Project
- Fondazione Cariplo [2019-3277, 2017-0535]
- Associazione Italiana Ricerca sul Cancro (AIRC, Milano) [IG 20714]
- Fondazione Amici di Jean (Torino)
- National Ministry of University and research PRIN 2017 [201799WCRH]
- Consorzio Interuniversitario di Biotecnologie (CIB) bando Network-CIB: Catalisi dell'Innovazione nelle biotecnologie
ICOSL/ICOS are costimulatory molecules pertaining to immune checkpoints; their binding transduces signals having anti-tumor activity. Osteopontin (OPN) is here identified as a ligand for ICOSL. OPN binds a different domain from that used by ICOS, and the binding induces a conformational change in OPN, exposing domains that are relevant for its functions. Here we show that in vitro, ICOSL triggering by OPN induces cell migration, while inhibiting anchorage-independent cell growth. The mouse 4T1 breast cancer model confirms these data. In vivo, OPN-triggering of ICOSL increases angiogenesis and tumor metastatization. The findings shed new light on ICOSL function and indicate that another partner beside ICOS may be involved; they also provide a rationale for developing alternative therapeutic approaches targeting this molecular trio. Davide Raineri, Chiara Dianzani et al. show that osteopontin binds ICOSL at a different domain than the one used by ICOS. Activation of ICOSL by osteopontin induces cell migration in vitro and tumor metastatization in a 4T1 breast cancer mouse model; highlighting the functional role of this interaction in cancer progression.
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