| Title | Extracellular vesicles from the lung pro-thrombotic niche drive cancer-associated thrombosis and metastasis via integrin beta 2. |
| Publication Type | Journal Article |
| Year of Publication | 2025 |
| Authors | Lucotti S, Ogitani Y, Kenific CM, Geri J, Kim YHun, Gu J, Balaji U, Bojmar L, Shaashua L, Song Y, Cioffi M, Lauritzen P, Joseph OM, Asao T, Grandgenett PM, Hollingsworth MA, Peralta C, Pagano AE, Molina H, Lengel HB, Dunne EG, Jing X, Schmitter M, Borriello L, Miller T, Zhang H, Romin Y, Manova K, Paul D, H Remmel L, O'Reilly EM, Jarnagin WR, Kelsen D, Castellino SM, Giulino-Roth L, Jones DR, Condeelis JS, Pascual V, Bussel JB, Boudreau N, Matei I, Entenberg D, Bromberg JF, Simeone DM, Lyden D |
| Journal | Cell |
| Date Published | 2025 Feb 10 |
| ISSN | 1097-4172 |
| Abstract | Cancer is a systemic disease with complications beyond the primary tumor site. Among them, thrombosis is the second leading cause of death in patients with certain cancers (e.g., pancreatic ductal adenocarcinoma [PDAC]) and advanced-stage disease. Here, we demonstrate that pro-thrombotic small extracellular vesicles (sEVs) are secreted by C-X-C motif chemokine 13 (CXCL13)-reprogrammed interstitial macrophages in the non-metastatic lung microenvironment of multiple cancers, a niche that we define as the pro-thrombotic niche (PTN). These sEVs package clustered integrin β2 that dimerizes with integrin αX and interacts with platelet-bound glycoprotein (GP)Ib to induce platelet aggregation. Blocking integrin β2 decreases both sEV-induced thrombosis and lung metastasis. Importantly, sEV-β2 levels are elevated in the plasma of PDAC patients prior to thrombotic events compared with patients with no history of thrombosis. We show that lung PTN establishment is a systemic consequence of cancer progression and identify sEV-β2 as a prognostic biomarker of thrombosis risk as well as a target to prevent thrombosis and metastasis. |
| DOI | 10.1016/j.cell.2025.01.025 |
| Custom 1 | |
| Alternate Journal | Cell |
| PubMed ID | 39938515 |