Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology.
Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology.
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DOI：
10.4161/cbt.9.1.10378
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发表时间：
2010-01
影响因子：
3.6
通讯作者：
Hendrix MJ
中科院分区：
文献类型：
--
作者：
Abbott DE;Margaryan NV;Jeruss JS;Khan S;Kaklamani V;Winchester DJ;Hansen N;Rademaker A;Khalkhali-Ellis Z;Hendrix MJ
组织蛋白酶D是一种参与细胞内和细胞外蛋白水解的溶酶体水解酶。这种酶在恶性肿瘤中异常产生和加工，最值得注意的是过度分泌到肿瘤细胞微环境中。这种过度分泌可能导致细胞外基质的过度降解，并有助于肿瘤进展和转移。这些现象已经在体外建立，并且有证据表明组织蛋白酶D在人类乳腺癌患者中同样失调。由于乳腺癌缺乏有效的筛查或监测生物标志物，在这里，我们解决的假设，血清组织蛋白酶D活性可能是有用的，以评估女性乳腺癌的存在或进展。虽然来自各种疾病特异性队列的代表性组织学切片证实了先前的发现，即组织蛋白酶D的产生和分泌增加与肿瘤进展相关，但我们报告无疾病患者、浸润前或有限浸润性疾病患者和转移性疾病患者之间的血清组织蛋白酶D活性无差异。此外，在已知转移性疾病的患者中，没有与血清组织蛋白酶D活性显著不同相关的临床变量。然而，乳腺癌患者组织病理切片中组织蛋白酶D表达的免疫组织化学定位与疾病进展相关。基于血清结果，并且与乳腺癌组织中的组织蛋白酶D定位相反，我们的研究结果支持使用组织蛋白酶D作为疾病进展的可靠组织病理学生物标志物，但不用于血清筛查。
Cathepsin D is a lysosomal hydrolase involved in intra- and extracellular proteolysis. This enzyme is aberrantly produced and processed in malignancy, and most notably is over-secreted into the tumor cell microenvironment. This hyper-secretion may lead to excessive degradation of the extracellular matrix, and contribute to tumor progression and metastases. These phenomena have been established in vitro, and there is evidence that Cathepsin D is similarly dysregulated in human breast cancer patients. Because breast cancer lacks an effective screening or surveillance biomarker, here we address the hypothesis that serum Cathepsin D activity may be useful to assess the presence or progression of breast cancer in females. While representative histologic sections from various disease-specific cohorts confirm previous findings that increased Cathepsin D production and secretion correlate with tumor progression, we report no difference in serum Cathepsin D activity between patients who are disease-free, patients with pre-invasive or limited invasive disease, and patients with metastatic disease. Furthermore, in patients with known metastatic disease, there were no clinical variables associated with significantly different serum Cathepsin D activity. however, the immunohistochemical localization of Cathepsin D expression in histopathologic sections from breast cancer patients correlates with disease progression. Based on the serum results, and in contradistinction to Cathepsin D localization in breast cancer tissues, our findings support using Cathepsin D as a reliable histopathology biomarker for disease progression, but not for serum screening.
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影响因子：
3.8
作者：
ODONOGHUE, AEMA;POLLER, DN;ELLIS, IO
通讯作者：
ELLIS, IO
影响因子：
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作者：
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影响因子：
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作者：
PUJOL, P;MAUDELONDE, T;ROCHEFORT, H
通讯作者：
ROCHEFORT, H
影响因子：
4.4
作者：
Pitteri, Sharon J.;Faca, Vitor M.;Hanash, Samir M.
通讯作者：
Hanash, Samir M.
影响因子：
45.3
作者：
ISOLA, J;WEITZ, S;KALLIONIEMI, OP
通讯作者：
KALLIONIEMI, OP