Werle B, Kraft C, Lah T T, Kos J, Schanzenbächer U, Kayser K, Ebert W, Spiess E
Thoraxklinik Heidelberg gGmbH, Department of Clinical Chemistry and Bacteriology, Germany.
Cancer. 2000 Dec 1;89(11):2282-91.
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.
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.
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.
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.
肿瘤细胞侵袭和转移需要特定的蛋白水解酶，包括溶酶体肽酶——组织蛋白酶。组织蛋白酶B是一种溶酶体半胱氨酸肽酶，似乎在人类肿瘤的侵袭和转移中起主要作用。在本研究中，作者通过研究组织蛋白酶B在肺肿瘤及相应肿瘤浸润淋巴结中的酶定位及其活性，聚焦于其在淋巴转移中的可能作用。
测定同一患者的肺肿瘤、肺实质以及肿瘤细胞浸润和未浸润的区域淋巴结中的组织蛋白酶B活性。作者研究了35例非小细胞肺癌患者。通过在pH 6.0条件下切割荧光底物Z-Arg-Arg-AMC来测定组织蛋白酶B的总活性。
组织蛋白酶B的中位比活性在肿瘤中最高，其次是浸润淋巴结、未浸润淋巴结和肺实质。作者发现，与未浸润的区域淋巴结相比，肿瘤浸润淋巴结中的组织蛋白酶B活性显著增加了1.8倍，与肺实质相比，肺肿瘤组织中的组织蛋白酶B活性增加了4.5倍。肿瘤和肿瘤细胞浸润淋巴结中较高的组织蛋白酶B活性表明总生存期预后较差。免疫组织化学分析显示组织蛋白酶B存在于组织细胞和肿瘤细胞中，但不存在于淋巴结组织的淋巴细胞中。
作者关于肿瘤细胞浸润淋巴结中组织蛋白酶B水平较高的发现表明，组织蛋白酶B活性水平升高是侵袭性肿瘤细胞表型的特征。这证实了肿瘤细胞相关的组织蛋白酶B可能在淋巴转移中起作用这一假说。作者的结果支持将淋巴结相关的组织蛋白酶B用作肺癌患者生存的预后因素。
