Extracellular vesicles from the lung pro-thrombotic niche drive cancer-associated thrombosis and metastasis via integrin beta 2 Journal Article

  

Authors:	Lucotti, S.; Ogitani, Y.; Kenific, C. M.; Geri, J.; Kim, Y. H.; Gu, J.; Balaji, U.; Bojmar, L.; Shaashua, L.; Song, Y.; Cioffi, M.; Lauritzen, P.; Joseph, O. M.; Asao, T.; Grandgenett, P. M.; Hollingsworth, M. A.; Peralta, C.; Pagano, A. E.; Molina, H.; Lengel, H. B.; Dunne, E. G.; Jing, X.; Schmitter, M.; Borriello, L.; Miller, T.; Zhang, H.; Romin, Y.; Manova, K.; Paul, D.; Remmel, H. L.; O'Reilly, E. M.; Jarnagin, W. R.; Kelsen, D.; Castellino, S. M.; Giulino-Roth, L.; Jones, D. R.; Condeelis, J. S.; Pascual, V.; Bussel, J. B.; Boudreau, N.; Matei, I.; Entenberg, D.; Bromberg, J. F.; Simeone, D. M.; Lyden, D.
Article Title:	Extracellular vesicles from the lung pro-thrombotic niche drive cancer-associated thrombosis and metastasis via integrin beta 2
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. © 2025 Elsevier Inc.
Keywords:	platelets; cancer metastasis; cancer; extracellular vesicles; cancer-associated thrombosis; integrin beta 2; pro-thrombotic niche
Journal Title:	Cell
Volume:	188
Issue:	6
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2025-03-20
Start Page:	1642
End Page:	1661.e24
Language:	English
DOI:	10.1016/j.cell.2025.01.025
PUBMED:	39938515
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-86000363293&doi=10.1016%2fj.cell.2025.01.025&partnerID=40&md5=2e5de09c8d42518632cca7b6a71c238b
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Jaqueline Bromberg -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/223717