| First Author | Raineri D | Year | 2020 |
| Journal | Commun Biol | Volume | 3 |
| Issue | 1 | Pages | 615 |
| PubMed ID | 33106594 | Mgi Jnum | J:336899 |
| Mgi Id | MGI:6799195 | Doi | 10.1038/s42003-020-01333-1 |
| Citation | Raineri D, et al. (2020) Osteopontin binds ICOSL promoting tumor metastasis. Commun Biol 3(1):615 |
| abstractText | 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. |
