Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma

BACKGROUND. Tumor cells require specific proteolytic enzymes for invasion a nd metastasis, including lysosomal peptidases-cathepsins. Cathepsin B is a lysosomal cysteine peptidase, which appears to play a major role in invasio n and metastasis of human turners. In this study, the authors focused on th e possible role of cathepsin B in lymphogenic metastasis by investigating t he enzyme localization and its activity in lung tumors and corresponding tu mor-infiltrated lymph nodes. METHODS. Cathepsin B activity was determined in lung turners, lung parenchy ma, and tumor cell-infiltrated and noninfiltrated regional lymph nodes of t he same patient. The authors investigated 35 cancer patients suffering from nonsmall cell lung carcinoma. Cathepsin B throughout activity was measured by cleavage of the fluorogenic substrate Z-Arg-Arg-AMC at pH 6.0. RESULTS. The median specific cathepsin B activity was highest in tumors, fo llowed by the infiltrated lymph nodes, noninfiltrated lymph nodes, and lung parenchyma. The authors showed a significant 1.8-fold increase in cathepsi n B activity in turner-infiltrated lymph nodes compared with noninfiltrated regional lymph nodes and a 4.5-fold increase in lung tumor tissue compared with lung parenchyma. High cathepsin B activity, both in tumors and tumor cell-infiltrated lymph nodes, indicated poor prognosis for overall survival . Immunohistochemical analysis showed the presence of cathepsin B in histio cytes and tumor cells but not in lymphocytes of lymph node tissue. CONCLUSIONS. The authors' findings on higher cathepsin B levels in tumor ce ll-infiltrated lymph nodes show that increased level of cathepsin B activit y is characteristic of the invasive tumor cell phenotype. This corroborates the hypothesis, that tumor cell associated cathepsin B may play a role in lymphogenic metastasis. The authors' results support the use of lymph node associated cathepsin B as a prognostic factor for survival of patients with lung carcinoma. Cancer 2000;89: 2282-91. (C) 2000 American Cancer Society.