Stromal Cell Molecules Required for Lymphoma Generation

滤泡性淋巴瘤是成人最常见的血液系统恶性肿瘤之一，早期通常无痛，自发性消退，对化疗敏感。然而，这种肿瘤经常复发，并可经历原始转化为侵袭性形式，最终成为一种致命的疾病。该肿瘤的发生和转化与生发中心的滤泡树突状细胞(FDC)密切相关。本研究的目的是通过制备阻断FDC介导的淋巴瘤细胞增殖的FDC特异性单抗，在体内外鉴定FDC信号分子，并利用这些抗体从FDC细胞系HK的cDNA文库中克隆信号分子的基因。克隆的基因将通过在COS细胞中表达并在体外和体内实验模型中进行评估来研究其功能。将使用GC来源的人淋巴瘤细胞系L3055，因为该细胞系的生长依赖于FDC/HK在体外和体内的生长。识别淋巴瘤生长所需的基质细胞分子将导致拮抗剂的开发。这种拮抗剂可能具有巨大的治疗潜力，可以抑制恶性淋巴瘤或其他转移到淋巴滤泡的肿瘤的生长。

In the early stage, follicular lymphoma, one of the most common hematological malignancies in adults, is usually indolent, regressing spontaneously and showing susceptibility to chemotherapy. However, this tumor often recurs and can undergo blast transformation to an aggressive form, ultimately becoming a fatal disease. The generation and blast transformation of this tumor occur in close association with follicular dendritic cells (FDC) in the germinal center (GC). The objective is to identify the FDC signaling molecules by preparing the FDC-specific monoclonal antibodies that block FDC-mediated lymphoma cell proliferation in vitro and in vivo, and then use these antibodies to clone the genes of the signaling molecules from cDNA library of an FDC line, HK. The functions of the cloned genes will be investigated by expressing them in COS cells and evaluating them in in vitro and in vivo experimental models. A human lymphoma cell line of GC-origin, L3055, will be use, because growth of this cell line depends on FDC/HK in vitro and in vivo. Identification of the stromal cell molecules required for the growth of the lymphomageneses will lead to development of antagonists. Such antagonists may have a tremendous therapeutic potential to suppress the growth of malignant lymphomas or other tumors that metastasized to lymphoid follicles.