Cathepsin K mRNA and protein expression in prostate cancer progression
Cathepsin K mRNA and protein expression in prostate cancer progression
复制标题
DOI：
10.1359/jbmr.2003.18.2.222
复制
发表时间：
2003-02-01
影响因子：
6.2
通讯作者：
Corey, E
中科院分区：
文献类型：
--
作者：
Brubaker, KD;Vessella, RL;Corey, E
前列腺癌 (CaP) 是男性最常见的恶性肿瘤，通常与骨转移相关，而骨转移是与 CaP 相关的大部分发病原因。与 CaP 相关的病变通常表现出骨形成和吸收增加。骨吸收增加可能会从细胞外基质中释放有助于肿瘤生长的因子。组织蛋白酶 K (cat K) 是一种半胱氨酸蛋白酶，对细胞外基质表现出强烈的降解活性，并参与破骨细胞介导的骨破坏。在本研究中，我们分析了 Cat K 在 CaP 细胞系和患者样本中的表达。通过逆转录聚合酶链式反应 (RT-PCR) 在 CaP 细胞系中检测到 Cat K 信息，并通过原位杂交在原发性 CaP 和转移瘤中检测到 Cat K 信息。免疫组织化学显示原发性 CaP 样本以及非骨转移瘤中 cat K 的表达存在差异，而骨转移瘤中的表达显着高于原发性 CaP，而正常前列腺组织呈阴性。免疫沉淀后通过蛋白质印迹法在 CaP 细胞系中检测到 Cat K 蛋白。通过荧光测定和 I 型胶原蛋白降解测定，也检测到了 CaP 细胞系中的 Cat K 酶活性。在 CaP 骨转移患者的血清中也检测到了 NTx 水平的增加，NTx 是主要由 cat K 介导的骨基质降解标志物。我们假设 CaP 表达的 cat K 可能有助于 CaP 的侵袭潜力，而骨转移中表达的增加与基质降解的作用一致。
Prostate cancer (CaP) is the most commonly diagnosed malignancy in men and is often associated with bone metastases, which cause much of the morbidity associated with CaP. Lesions associated with CaP generally exhibit increased bone formation and resorption. Increased bone resorption may release factors from the extracellular matrix that contribute to tumor growth. Cathepsin K (cat K) is a cysteine protease that exhibits strong degradative activity against the extracellular matrix and is involved in osteoclast-mediated bone destruction. In this study, we analyzed the expression of cat K in CaP cell lines and patient samples. Cat K message was detected in CaP cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and in primary CaP and metastases by in situ hybridization. Immunohistochemistry revealed variable expression of cat K in primary CaP samples, as well as nonosseous metastases, whereas expression in bone metastases was significantly higher than in primary CaP, and normal prostate tissues were negative. Cat K protein was detected in CaP cell lines by Western blotting after immunoprecipitation. Cat K enzymatic activity was also detected in CaP cell lines by a fluorogenic assay and by an assay for degradation of collagen type I. Increased levels of NTx, a marker of bone matrix degradation mediated primarily by cat K, were also detected in sera of patients with CaP bone metastases. We hypothesize that CaP-expressed cat K may contribute to the invasive potential of CaP, while increased expression in bone metastases is consistent with a role in matrix degradation.