Brouillet J P, Spyratos F, Hacene K, Fauque J, Freiss G, Dupont F, Maudelonde T, Rochefort H
Unité Hormones et Cancer (U 148) INSERM, Montpellier, France.
Eur J Cancer. 1993;29A(9):1248-51. doi: 10.1016/0959-8049(93)90066-o.
In breast cancer cell lines, the maturation of pro-cathepsin D into enzymatically active cathepsin D is altered, leading to its increased secretion. In order to specifically assay pro-cathepsin D (52 kD form) in breast cancer cytosol, we monitored a solid phase sandwich radioimmunoassay using D9H8 and D7E3 monoclonal antibodies raised against human pro-cathepsin D from MCF7 cells. Pro-cathepsin D was assayed in 108 primary breast cancer cytosols in which total cathepsin D was previously found to be correlated with metastasis. Pro-cathepsin D concentrations were found to be correlated with total cathepsin D and with lymph node invasion, and was slightly higher in premenopausal patients. By contrast, Cox multiparametric analysis showed that pro-cathepsin D status had no prognostic value for survival, or metastasis free survival contrary to total cathepsin D status. This first study shows the technical validity of the pro-cathepsin D assay but indicates that it has less value as a prognostic marker than total cathepsin D. This study also shows that the proportion of pro-cathepsin D recovered in vivo (1-6%) is much less than that produced in cell lines and suggests that the secreted pro-enzyme might be activated in the tumour extracellularly or following its reinternalisation.
在乳腺癌细胞系中，组织蛋白酶原D向具有酶活性的组织蛋白酶D的成熟过程发生改变，导致其分泌增加。为了特异性检测乳腺癌细胞溶质中的组织蛋白酶原D（52kD形式），我们使用针对MCF7细胞来源的人组织蛋白酶原D产生的D9H8和D7E3单克隆抗体监测了一种固相夹心放射免疫测定法。在108例原发性乳腺癌细胞溶质中检测了组织蛋白酶原D，此前发现这些样本中总的组织蛋白酶D与转移相关。结果发现，组织蛋白酶原D的浓度与总的组织蛋白酶D以及淋巴结浸润相关，且在绝经前患者中略高。相比之下，Cox多参数分析表明，与总的组织蛋白酶D状态相反，组织蛋白酶原D状态对生存或无转移生存没有预后价值。这项首次研究表明了组织蛋白酶原D检测方法在技术上的有效性，但表明其作为预后标志物的价值低于总的组织蛋白酶D。该研究还表明，体内回收的组织蛋白酶原D的比例（1-6%）远低于细胞系中产生的比例，并提示分泌的酶原可能在肿瘤细胞外或重新内化后被激活。
