[The lysosomal cathepsins B, L and D in development of murine experimental leukemias]

Lysosomal proteases are actively involved in pathogenesis of cancer progression. Alterations in proteases and their inhibitors interaction were suggested to be implicated in the processes of tumor invasion and metastasis. Among proteases connected with malignant growth, cysteine cathepsins B and L and aspartic cathepsin D play the main role in the tumor development. The present study was designed to investigate activity of cathepsins B, L and D activity in the development and treatment of murine experimental leukemias and to determine the correlation of these proteases with tumor malignancy and the chemotherapy effect. P-388 leukemia was characterized by a more aggressive development and unfavorable prognosis than L1210/1 leukemia. The activity of cathepsins B, L and D in tumor tissues of mice infected with P-388 leukemia, as well as in liver and spleen and the activity of cathepsins B and L in serum were lower than their activity in mice infected with L1210/1 leukemia. Changes of cathepsin activity in liver and spleen of mice with leukemias have demonstrated a level of aggressiveness of tumor development and invasion of liver and spleen by neoplastic cells. The treatment resulted in the increase of cathepsin B, L and D activities in tumor tissue, liver, spleen and cathepsin B and L activities in serum. The highest activity of proteases was revealed in the groups of mice characterized by the greatest suppression of tumor growth. These data have shown that lysosomal proteases are involved in progression of murine experimental leukemias and elimination of tumor cells in the result of treatment. Determination of the activity of cysteine and aspartic proteases can be used for evaluation of cancer diseases malignancy, their sensitivity for chemotherapy and efficiency of treatment.