Cathepsins B, H, L and cysteine protease inhibitors in malignant prostate cell lines, primary cultured prostatic cells and prostatic tissue
Cathepsins B, H, L and cysteine protease inhibitors in malignant prostate cell lines, primary cultured prostatic cells and prostatic tissue
复制标题
DOI：
10.1016/s0959-8049(98)00273-1
复制
发表时间：
1999-01-01
影响因子：
8.4
通讯作者：
Loening, SA
中科院分区：
文献类型：
--
作者：
Friedrich, B;Jung, K;Loening, SA
半胱氨酸蛋白酶、组织蛋白酶B、H、L(CB、CH、CL)和半胱氨酸蛋白酶抑制物(CPI)活性升高在多种肿瘤中被证实，并被认为与肿瘤的侵袭和转移有关。前列腺癌的情况仍然未知。本研究用荧光分光光度法检测了根治性前列腺癌、腺瘤切除、经尿道前列腺电切术后前列腺组织中CB、CN、CL的催化活性，以及前列腺癌和非癌组织中CB、CN、CL的催化活性，以及LNCaP、DU 145和PC 3细胞系中CB、CN、CL的催化活性。比较来自正常前列腺和前列腺癌组织的配对样本，发现前列腺癌组织中CB、CL的水平显著降低。相比之下，来自癌症样本的原代细胞培养显示，与来自正常前列腺的细胞培养相比，CB、CH、CL水平升高，组织蛋白与CPI的比率增加。已建立的细胞系呈现出相似的组织蛋白酶分布模式，其中DU 145的含量最高，其次是LNCaP和PC 3。我们的结果表明，前列腺癌和非癌部分原代细胞培养中组织蛋白酶水平的升高以及由此导致的组织蛋白酶/CPI的比值增加可能表明前列腺癌细胞中存在细胞蛋白分解失衡。在这方面，原代细胞培养实验应该比组织样本中的测定更可取。(C)1999爱思唯尔科学有限公司。保留所有权利。
Elevated activities of cysteine proteinases, the cathepsins B, H, L (CB, CH, CL) and diminished cysteine protease inhibitors (CPI) have been demonstrated in a variety of tumours and have been suggested to contribute to invasion and metastasis. The situation for prostate cancer is still unknown. In this study, using fluorimetric assays, the catalytic activities of CB, CN, CL were measured in prostatic tissue samples after radical prostatectomy, adenomectomy, transurethral resection of the prostate, in cell cultures grown from cancerous and non-cancerous parts of human prostate after prostatectomy and in the cell lines LNCaP, DU 145 and PC 3. CPIs were determined using heat activation before testing their inhibitory activity against purified CB. Comparing matched pairs of normal and cancerous tissue samples from the prostate, significantly decreased levels of CB, CL in malignant parts of the prostate were found. In contrast, primary cell cultures from cancerous samples showed elevated levels of CB, CH, CL and increased ratios of cathepsins to CPI compared with cell cultures from normal prostate. Established cell lines showed a similar distribution pattern of each cathepsin, DU 145 containing the highest levels, followed by LNCaP and PC 3. Our results suggest that elevated cathepsin levels and consequently increased ratios of cathepsins to CPI in primary cell cultures from cancerous versus non-cancerous parts of the prostate may be indicative of a cellular proteolytic imbalance in prostatic cancer cells. In this respect, primary cell culture experiments should be preferred to determinations in tissue samples. (C) 1999 Elsevier Science Ltd. All rights reserved.