MITOGENIC FUNCTION OF HUMAN PROCATHEPSIN-D - THE ROLE OF THE PROPEPTIDE
MITOGENIC FUNCTION OF HUMAN PROCATHEPSIN-D - THE ROLE OF THE PROPEPTIDE
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DOI：
10.1042/bj3030775
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发表时间：
1994-11-01
影响因子：
4.1
通讯作者：
VETVICKA, V
中科院分区：
文献类型：
--
作者：
FUSEK, M;VETVICKA, V
一些人类乳腺癌细胞系在雌激素刺激下会分泌组织蛋白酶 D 的前体。在这些细胞系中，组织蛋白酶 D 被描述为自分泌有丝分裂原，并且肿瘤组织中的组织蛋白酶 D 浓度与患者不良预后之间的相关性已在多项独立研究中得到证实。在本研究中，我们重点研究组织蛋白酶 D 促有丝分裂活性的机制。从 ZR-75-1 乳腺癌细胞系分泌物中分离出的组织蛋白酶 D 被用来测试七种人类细胞系的促有丝分裂活性。对于纳摩尔组织蛋白酶 D 浓度，我们发现在几种不同的人类乳腺癌衍生细胞系中存在更强的剂量反应性细胞反应。有丝分裂活性不被蛋白水解活性的抑制或组织蛋白酶原 D 与 6-磷酸甘露糖受体相互作用的抑制所阻断。另一方面，添加针对前肽产生的抗体会损害组织蛋白酶D原的促有丝分裂活性，并且单独对应于组织蛋白酶D前肽的合成肽产生类似的效果，酶原分子也是如此。合成前肽可部分阻断组织蛋白酶 D 与细胞表面的相互作用。我们的结果表明，促有丝分裂功能涉及组织蛋白酶 D 的前肽，该前肽似乎被表面受体识别。
The proform of cathepsin D is secreted by some human breast-cancer cell lines upon stimulation with oestrogen. In these cell lines, procathepsin D was described to act as an autocrine mitogen, and a correlation between the cathepsin D concentration in tumour tissues and poor prognosis for the patient was demonstrated in several independent investigations. In the present study, we focused on the mechanism of procathepsin D mitogenic activity. Procathepsin D isolated from secretions of ZR-75-1 breast-cancer cell line was used to test for mitogenic activity on a set of seven human cell lines. For nanomolar procathepsin D concentrations, we found a stronger dose-responsive cellular reaction in the case of several different human breast-cancer-derived cell lines. The mitogenic activity was not blocked by the inhibition of proteolytic activity nor by the inhibition of the interaction of procathepsin D with mannose-6-phosphate receptors. On the other hand, the addition of antibodies raised against the propeptide impaired the mitogenic activity of procathepsin D, and a synthetic peptide alone cor responding to the propeptide of procathepsin D produced similar effects, as did the zymogen molecule. The synthetic propeptide was shown to block partially the interaction of procathepsin D with the cellular surface. Our results indicate that the mitogenic function involves the propeptide of cathepsin D, which appears to be recognized by a surface receptor.