JAM-A as a prognostic factor and new therapeutic target in multiple myeloma

• Published in: Leukemia Vol. 32; no. 3; pp. 736 - 743
• Main Authors: Solimando, A G, Brandl, A, Mattenheimer, K, Graf, C, Ritz, M, Ruckdeschel, A, Stühmer, T, Mokhtari, Z, Rudelius, M, Dotterweich, J, Bittrich, M, Desantis, V, Ebert, R, Trerotoli, P, Frassanito, M A, Rosenwald, A, Vacca, A, Einsele, H, Jakob, F, Beilhack, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2018; Nature Publishing Group
• Subjects: 13/1; 13/31; 13/51; 14/5; 14/63; 64/60; 692/699/67/1990; 692/699/67/1990/804; 96/34; Adhesion; Biomarkers; Bone marrow; Cancer Research; Cell adhesion; Cell adhesion & migration; Cell migration; Cell survival; Chemotaxis; Critical Care Medicine; Drug resistance; Hematology; Intensive; Internal Medicine; Jamming; Medical prognosis; Medicine; Medicine & Public Health; Monoclonal antibodies; Multiple myeloma; Oncology; Original; original-article; Plasma cells; Therapeutic applications; Therapeutic targets; Viability; Xenografts; Xenotransplantation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2017.287

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.