Department of Internal Medicine II, Interdisciplinary Center for Clinical Research Laboratory, University Hospital of Würzburg, Würzburg, Germany.
Division of Hematology and Oncology, Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
Leukemia. 2018 Mar;32(3):736-743. doi: 10.1038/leu.2017.287. Epub 2017 Sep 28.
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.
多发性骨髓瘤（MM）微环境中的细胞黏附已被认为是 MM 细胞存活和耐药性发展的主要机制。在这里，我们提出了一个假设，即蛋白连接黏附分子-A（JAM-A）可能代表 MM 中的一个新靶点和临床生物标志物。我们评估了 JAM-A 在 MM 细胞系和 147 例 MM 患者不同疾病阶段的骨髓抽吸物和活检中的表达。患者来源的浆细胞中 JAM-A 水平升高与预后不良相关。此外，与对照组相比，MM 患者的循环可溶性 JAM-A（sJAM-A）水平显著升高。值得注意的是，体外 JAM-A 抑制可损害 MM 细胞的迁移、集落形成、趋化性、增殖和活力。在 MM 小鼠异种移植模型中，用抗-JAM-A 单克隆抗体（αJAM-A moAb）进行体内治疗可损害肿瘤进展。这些结果表明，JAM-A 的治疗靶向有可能预防 MM 的进展，并促使我们提出 JAM-A 作为 MM 的生物标志物，以及 sJAM-A 作为基于血清的临床分层标志物。
