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.

Osteopontin binds ICOSL promoting tumor metastasis / Raineri, D.; Dianzani, C.; Cappellano, G.; Maione, F.; Baldanzi, G.; Iacobucci, I.; Clemente, N.; Baldone, G.; Boggio, E.; Gigliotti, C. L.; Boldorini, R.; Rojo, J. M.; Monti, M.; Birolo, L.; Dianzani, U.; Chiocchetti, A.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 3:1(2020), p. 615. [10.1038/s42003-020-01333-1]

Osteopontin binds ICOSL promoting tumor metastasis

Iacobucci I.;Monti M.;Birolo L.;
2020

Abstract

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.
2020
Osteopontin binds ICOSL promoting tumor metastasis / Raineri, D.; Dianzani, C.; Cappellano, G.; Maione, F.; Baldanzi, G.; Iacobucci, I.; Clemente, N.; Baldone, G.; Boggio, E.; Gigliotti, C. L.; Boldorini, R.; Rojo, J. M.; Monti, M.; Birolo, L.; Dianzani, U.; Chiocchetti, A.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 3:1(2020), p. 615. [10.1038/s42003-020-01333-1]
File in questo prodotto:
File Dimensione Formato  
CommBiol_OPN_2020.pdf

accesso aperto

Tipologia: Documento in Post-print
Licenza: Accesso privato/ristretto
Dimensione 2.55 MB
Formato Adobe PDF
2.55 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/820821
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 35
social impact