Rochefort H, Capony F, Garcia M
Unité Hormones et Cancer (U 148) INSERM, University of Montpellier, France.
Cancer Metastasis Rev. 1990 Dec;9(4):321-31. doi: 10.1007/BF00049522.
Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, via possibly saturation of the Man-6-P/IGF-II receptor, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in axillary node-negative tumors. Transfection of a human cDNA cathepsin D expression vector under the control of SV40 promoter increases the metastatic potential of 3YA1-Ad12 rat tumorigenic cells when intravenously injected into nude mice. The mechanism of cathepsin D-induced metastasis is currently unknown. These results indicate that overexpression of cathepsin D might facilitate breast cancer metastasis, suggesting new possible therapeutic approaches.
组织蛋白酶D是一种存在于所有细胞中的酸性溶酶体蛋白酶。在雌激素受体阳性和阴性的乳腺癌细胞系中，编码组织蛋白酶D原的mRNA过度表达，且该酶原的分选和成熟过程发生改变，这可能是由于甘露糖-6-磷酸/胰岛素样生长因子II受体饱和所致，从而导致活性蛋白酶在大的内体中积累以及前体（52K蛋白）的分泌。在MCF7细胞中，组织蛋白酶D的mRNA由雌激素直接转录诱导，并由生长因子间接诱导。在患者中，原发性乳腺癌细胞溶质中高浓度的组织蛋白酶D与转移的发生显著相关。该标志物独立于其他预后因素，在腋窝淋巴结阴性肿瘤中似乎特别有用。当将在SV40启动子控制下的人组织蛋白酶D cDNA表达载体转染的3YA1-Ad12大鼠致瘤细胞静脉注射到裸鼠体内时，其转移潜能会增加。目前尚不清楚组织蛋白酶D诱导转移的机制。这些结果表明，组织蛋白酶D的过度表达可能促进乳腺癌转移，提示了新的可能治疗方法。
