Stromal Cell Molecules Required for Lymphoma Generation

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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.