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.

中文翻译：

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JAM-A是多发性骨髓瘤的预后因素和新的治疗靶标。

在多发性骨髓瘤（MM）微环境中的细胞粘附已被认为是MM细胞存活和耐药性发展的主要机制。在这里，我们解决了一个假设，即蛋白结合粘附分子-A（JAM-A）可能代表MM中的一个新的靶标和临床生物标志物。我们在不同疾病阶段评估了MM细胞系以及147 MM患者骨髓穿刺和活检中的JAM-A表达。患者来源的浆细胞中JAM-A水平升高与不良预后相关。此外，与对照组相比，MM患者的循环可溶性JAM-A（sJAM-A）水平显着增加。值得注意的是，体外JAM-A抑制作用会损害MM的迁移，菌落形成，趋化性，增殖和生存能力。在鼠异种移植MM模型中，抗JAM-A单克隆抗体（αJAM-AmoAb）的体内治疗会损害肿瘤的进展。这些结果表明，针对JAM-A的治疗靶向具有预防MM进展的潜力，并促使我们提出JAM-A作为MM中的生物标志物，而sJAM-A作为临床分层中基于血清的标志物。