دورية أكاديمية
Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression
| العنوان: | Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression |
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| المؤلفون: | Antonio G. Solimando, Matteo C. Da Vià, Patrizia Leone, Paola Borrelli, Giorgio A. Croci, Paula Tabares, Andreas Brandl, Giuseppe Di Lernia, Francesco P. Bianchi, Silvio Tafuri, Torsten Steinbrunn, Alessandra Balduini, Assunta Melaccio, Simona De Summa, Antonella Argentiero, Hilka Rauert-Wunderlich, Maria A. Frassanito, Paolo Ditonno, Erik Henke, Wolfram Klapper, Roberto Ria, Carolina Terragna, Leo Rasche, Andreas Rosenwald, K. Martin Kortüm, Michele Cavo, Domenico Ribatti, Vito Racanelli, Hermann Einsele, Angelo Vacca, Andreas Beilhack |
| المصدر: | Haematologica, Vol 106, Iss 7 (2020) |
| بيانات النشر: | Ferrata Storti Foundation, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases in the bone marrow (BM), we investigated whether BM MM endothelial cells (MMECs) control disease progression via the junctional adhesion molecule A (JAM-A). Membrane and cytoplasmic JAM-A levels were upregulated in MMECs in 111 newly diagnosed (NDMM) and 201 relapsed-refractory (RRMM) patients compared to monoclonal gammopathy of undetermined significance (MGUS) and healthy controls. Elevated membrane expression of JAM-A on MMECs predicted poor clinical outcome. Mechanistically, addition of recombinant JAM-A to MMECs increased angiogenesis whereas its inhibition impaired angiogenesis and MM growth in 2D and 3D in vitro cell culture and chorioallantoic membrane-assays. To corroborate these findings, we treated MM bearing mice with JAM-A blocking mAb and demonstrated impaired MM progression corresponding to decreased MM-related vascularity. These findings support JAM-A as an important mediator of MM progression through facilitating MM-associated angiogenesis. Collectively, elevated JAM-A expression on bone marrow endothelial cells is an independent prognostic factor for patient survival in both NDMM and RRMM. Blocking JAM-A restricts angiogenesis in vitro, in embrio and in vivo and represents a suitable druggable molecule to halt neoangiogenesis and MM progression. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/9777; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2019.239913 |
| URL الوصول: | https://doaj.org/article/c2545760d0c3467b8997b010e53370db |
| رقم الأكسشن: | edsdoj.2545760d0c3467b8997b010e53370db |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2019.239913 |