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Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma
Author(s) -
Werle Bernd,
Kraft Clemens,
Lah Tamara T.,
Kos Janko,
Schanzenbächer Ulrike,
Kayser Klaus,
Ebert Werner,
Spiess Eberhard
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20001201)89:11<2282::aid-cncr17>3.0.co;2-4
Subject(s) - cathepsin b , pathology , lymph , cathepsin , medicine , metastasis , parenchyma , cathepsin l , lymph node , lung cancer , cancer research , cancer , biology , enzyme , biochemistry
Abstract BACKGROUND Tumor cells require specific proteolytic enzymes for invasion and metastasis, including lysosomal peptidases—cathepsins. Cathepsin B is a lysosomal cysteine peptidase, which appears to play a major role in invasion and metastasis of human tumors. In this study, the authors focused on the possible role of cathepsin B in lymphogenic metastasis by investigating the enzyme localization and its activity in lung tumors and corresponding tumor‐infiltrated lymph nodes. METHODS Cathepsin B activity was determined in lung tumors, lung parenchyma, and tumor cell–infiltrated and noninfiltrated regional lymph nodes of the 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, followed by the infiltrated lymph nodes, noninfiltrated lymph nodes, and lung parenchyma. The authors showed a significant 1.8‐fold increase in cathepsin B activity in tumor‐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 histiocytes and tumor cells but not in lymphocytes of lymph node tissue. CONCLUSIONS The authors' findings on higher cathepsin B levels in tumor cell–infiltrated lymph nodes show that increased level of cathepsin B activity 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. © 2000 American Cancer Society.