Osteopontin binds ICOSL promoting tumor metastasis.

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.

Citation

Davide Raineri, Chiara Dianzani, Giuseppe Cappellano, Federica Maione, Gianluca Baldanzi, Ilaria Iacobucci, Nausicaa Clemente, Giulia Baldone, Elena Boggio, Casimiro L Gigliotti, Renzo Boldorini, Josè M Rojo, Maria Monti, Leila Birolo, Umberto Dianzani, Annalisa Chiocchetti. Osteopontin binds ICOSL promoting tumor metastasis. Communications biology. 2020 Oct 26;3(1):615

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PMID: 33106594

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