JAM-A as a prognostic factor and new therapeutic target in multiple myeloma
Solimando AG, Brandl A, Mattenheimer K, Graf C, Ritz M, Ruckdeschel A, Stuehmer T, Mokhtari Z, Rudelius M, Dotterweich J, Bittrich M, Desantis V, Ebert R, Trerotoli P, Frassanito MA, Rosenwald A, Vacca A, Einsele H, Jakob F, Beilhack A (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 32
Pages Range: 736-743
Journal Issue: 3
DOI: 10.1038/leu.2017.287
Abstract
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.
Involved external institutions
Universitätsklinikum Würzburg
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
University of Bari Aldo Moro / Università degli Studi di Bari Aldo Moro
Italy (IT)
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
University of Bari Aldo Moro / Università degli Studi di Bari Aldo Moro
Italy (IT)
How to cite
APA:
Solimando, A.G., Brandl, A., Mattenheimer, K., Graf, C., Ritz, M., Ruckdeschel, A.,... Beilhack, A. (2018). JAM-A as a prognostic factor and new therapeutic target in multiple myeloma. Leukemia, 32(3), 736-743. https://doi.org/10.1038/leu.2017.287
MLA:
Solimando, A. G., et al. "JAM-A as a prognostic factor and new therapeutic target in multiple myeloma." Leukemia 32.3 (2018): 736-743.
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