@article{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_2021, place={Pavia, Italy}, title={Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression}, volume={106}, url={https://haematologica.org/article/view/9777}, DOI={10.3324/haematol.2019.239913}, abstractNote={<p>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.</p&gt;}, number={7}, journal={Haematologica}, author={Antonio G. Solimando and Matteo C. Da Vià and Patrizia Leone and Paola Borrelli and Giorgio A. Croci and Paula Tabares and Andreas Brandl and Giuseppe Di Lernia and Francesco P. Bianchi and Silvio Tafuri and Torsten Steinbrunn and Alessandra Balduini and Assunta Melaccio and Simona De Summa and Antonella Argentiero and Hilka Rauert-Wunderlich and Maria A. Frassanito and Paolo Ditonno and Erik Henke and Wolfram Klapper and Roberto Ria and Carolina Terragna and Leo Rasche and Andreas Rosenwald and K. Martin Kortüm and Michele Cavo and Domenico Ribatti and Vito Racanelli and Hermann Einsele and Angelo Vacca and Andreas Beilhack}, year={2021}, month={Jul.}, pages={1943-1956} }