The long-term objective is to understand the role of adhesion molecules in the pathogenesis of non-Hodgkin's lymphomas. The proposed research focuses on the expression and function of adhesion molecules from patients with different cell types and stages of lymphomas. The profile of cell surface adhesion molecules on lymphoma cells will be established by use of a panel of monoclonal antibodies specific for different adhesion proteins. Adhesion inducing or blocking reagents such as monoclonal antibodies or pharmacologic reagents will be used to determine the functional capacity of cellular adhesion molecules in a variety of adhesion assays such as lymphoma cell adhesion to vascular endothelial and bone marrow stromal cells, extracellular matrix components, and other lymphoma cells. In addition, the hypothesis that serum levels of soluble adhesion molecules may correlate with disease stage or tumor burden will be tested. Serum from normal individuals and patients will be measured and compared by competitive inhibition assays or by a quantitative ELISA. From the foundation of data obtained from the analysis of lymphoma-associated adhesion molecules, a comprehensive definition of the adhesion molecules that delineate discrete stages of non-Hodgkin's lymphomas may be determined. These markers will be correlated with patient tumor burden and relapse to determine whether serum levels of soluble adhesion molecules reflect clinical stage at presentation and clinical outcome, and thus may also be used to monitor patient response to therapy. Ultimately, the identification of lymphoma indicative cell adhesion molecules should allow the development of rational approaches for devising new diagnostic tests and therapeutic regimens as well as to initiate mechanistic studies concerning organ localization, cell recirculation, positive and negative proliferation signals, and immune system evasion.
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