Hematology Service, University Hospital, Geneva, Switzerland; and.
Department of Pathology and Immunology, University Medical Center, Geneva University, Switzerland
J Leukoc Biol. 2016 Nov;100(5):843-853. doi: 10.1189/jlb.1HI1114-549RR. Epub 2016 Jun 2.
Junctional adhesion molecule (JAM)-C is a member of the JAM family, expressed by a variety of different cell types, including human B lymphocytes and some B-cell lymphoma subtypes-in particular, mantle cell lymphoma (MCL). Treatment with anti-JAM-C pAbs reduces homing of human B cells to lymphoid organs in a NOD/SCID mouse model. In the present study, the role of JAM-C in the engraftment of human lymphoma B cells in mice was investigated. Administration of novel anti-JAM-C mAbs reduced tumor growth of JAM-C MCL cells in bone marrow, spleen, liver, and lymph nodes of mice. Treatment with anti-JAM-C antibodies significantly reduced the proliferation of JAM-C-expressing lymphoma B cells. Moreover, the binding of anti-JAM-C antibodies inhibited the phosphorylation of ERK1/2, without affecting other signaling pathways. The results identify for the first time the intracellular MAPK cascade as the JAM-C-driven signaling pathway in JAM-C B cells. Targeting JAM-C could constitute a new therapeutic strategy reducing lymphoma B-cell proliferation and their capacity to reach supportive lymphoid microenvironments.
连接黏附分子（JAM）-C 是 JAM 家族的成员，由多种不同的细胞类型表达，包括人类 B 淋巴细胞和某些 B 细胞淋巴瘤亚型-特别是套细胞淋巴瘤（MCL）。用抗 JAM-C pAb 治疗可减少 NOD/SCID 小鼠模型中人类 B 细胞向淋巴器官的归巢。在本研究中，研究了 JAM-C 在小鼠中人类淋巴瘤 B 细胞植入中的作用。新型抗 JAM-C mAb 的给药可减少 JAM-C MCL 细胞在骨髓、脾脏、肝脏和淋巴结中的肿瘤生长。用抗 JAM-C 抗体治疗可显著降低 JAM-C 表达的淋巴瘤 B 细胞的增殖。此外，抗 JAM-C 抗体的结合抑制了 ERK1/2 的磷酸化，而不影响其他信号通路。这些结果首次确定了细胞内 MAPK 级联反应是 JAM-C 驱动的 JAM-C B 细胞中的信号通路。靶向 JAM-C 可能构成一种新的治疗策略，可减少淋巴瘤 B 细胞的增殖及其到达支持性淋巴微环境的能力。
