Tumoral CD24 tunes platelets binding and pro-metastatic functions

Mittelheisser, V.; Liboni, C.; Mouriaux, C.; Trivigno, S. M. G.; Bochler, L.; Garcia-Leon, M.; Larnicol, A.; Paulen, L.; Stemmelen, T.; Mangin, P. H.; Lefebvre, O.; GOETZ, J. G.

doi:10.1101/2025.04.09.648049

bioRxiv · 10.1101/2025.04.09.648049

Tumoral CD24 tunes platelets binding and pro-metastatic functions

Mittelheisser, V.·Liboni, C.·Mouriaux, C.·Trivigno, S. M. G.·Bochler, L.·Garcia-Leon, M.·Larnicol, A.·Paulen, L.·Stemmelen, T.·Mangin, P. H.·Lefebvre, O.·GOETZ, J. G.

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Abstract

One of the earliest steps of breast cancer metastasis occurs when tumor cells (TCs) disseminate through the bloodstream. There, they interact with several blood components. Among them, platelet favor TC survival and metastatic spread. While the binding of platelet to TC is highly variable, its molecular controls and downstream consequences remain unidentified. Here, we first document that high CD24 expression correlates with increased platelet binding and poorer survival in breast cancer. We further demonstrate that CD24-mediated platelet binding regulates TC cluster formation and resistance to anoikis in vitro. Depleting CD24 expression significantly reduces TC metastatic potential by rewiring the metastatic tumor microenvironment (mTME), affecting immune compartments and secreted factors. Overall, our work identifies CD24 as a molecular cue controlling TC-platelet interaction, dictating their metastatic potential. As such, it represents a druggable target to counteract platelet-TC collaboration in metastasis.

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Mittelheisser, V., Liboni, C., Mouriaux, C., Trivigno, S. M. G., Bochler, L., Garcia-Leon, M., Larnicol, A., Paulen, L., Stemmelen, T., Mangin, P. H., Lefebvre, O., GOETZ, J. G.. 2025-04-15. Tumoral CD24 tunes platelets binding and pro-metastatic functions. https://doi.org/10.1101/2025.04.09.648049

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