DISTINCT PATTERNS OF UROKINASE RECEPTOR (UPAR) EXPRESSION BY LEUKEMIC-CELLS AND PERIPHERAL-BLOOD CELLS

The urinary type plasminogen activator, urokinase (uPA) is localized o n the cell surface through the binding of a specific receptor, the uPA receptor (uPAR). The uPA localization enhances plasmin formation on t he cell surface and facilitates cell migration. The cellular and tissu e distribution of uPAR is not fully established. We have analyzed uPAR expression in nine leukemic cell lines of distinct lineages and matur ational states and correlated this with expression of plasminogen rece ptors, tissue-type plasminogen activator (tPA) receptors and LDL recep tor-related protein (LRP). The most immature arid least differentiated cell line (an erythro-myeloid cell line) and cells of lymphoid lineag e, did not express uPAR, whereas cells differentiated. ed along the my elo-monocytic pathway displayed this receptor. Plasminogen and tPA rec eptors were expressed by all leukemic cell lines and by all nucleated peripheral blood cells but B and T lymphocytes were negative for cell surface expression of both uPAR and LRP while monocytes and neutrophil s were positive for expression of both uPAR and LRP. PMA stimulation i nduced surface expression of uPAR in lymphocytes but did not induce ex pression of LRP by these cells. In contrast, lymphoid cell lines were negative for uPAR expression even after PMA stimulation, indicating di fferences in regulation of uPAR expression between lymphocytes and lym phoid cell lines. The pattern of uPAR expression on leukemic cell line s was also studied on bone marrow blast cells from leukemic patients. Only the most mature myeloid cells expressed uPAR on their surfaces. I n contrast, M3 leukemic cells and other blast cells displaying lymphoi d markers such as TdT (+) and/or CD2 (+) did not express intracellular or cell-surface associated uPAR, indicating an heterogeneity among th ese promyelocytic cells and suggesting that uPAR may be a useful marke r for leukemia typing. Myeloid blast cells from some patients containe d intracellular pools of uPAR but displayed no receptor on the cell su rface, suggesting that translocation may be a mechanism regulating uPA R expression in these cells. The comparison of uPAR expression between these cell lines and peripheral blood cells and it correlation with p lasminogen receptors, tPA receptors and LRP expression offers new insi ghts regarding potential mechanisms for regulation of uPA-uP-AR-mediat ed pericellular proteolysis.