Miyagi E, Yasumitsu H, Hirahara F, Minaguchi H, Koshikawa N, Miyazaki K, Umeda M
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University.
Jpn J Cancer Res. 1995 Jun;86(6):568-76. doi: 10.1111/j.1349-7006.1995.tb02436.x.
Matrix-degrading proteinases secreted by tumor cells play crucial roles in tumor cell invasion and metastasis. Serum-free conditioned media of 7 human gynecological carcinoma cell lines were examined for proteinases and their inhibitors by using gelatin zymography, reverse zymography and immunoblotting. All of three ovarian adenocarcinoma cell lines secreted urokinase-type plasminogen activator. Among them, a mucinous cystadenocarcinoma cell line also secreted tissue-type plasminogen activator, plasmin-like enzyme and trypsinogen. On the other hand, two ovarian undifferentiated carcinoma cell lines mainly secreted glatinase A or B. A choriocarcinoma cell line secreted multiple metalloproteinases in the highest amount, whereas an endometrial adenocarcinoma cell line (HEC-1) derived from an early clinical stage hardly secreted any gelatinolytic enzyme. The five high proteinases producers hardly secreted the corresponding inhibitors, such as tissue inhibitor of metalloproteinases (TIMP)-1, -2 or plasminogen activator inhibitor-1. In contrast to these highly malignant cell lines, a poor proteinase producer, HEC-1, secreted a large amount of TIMPs. Therefore, an enhanced proteolytic tendency appears to be associated with gynecological cancer cells established from highly malignant tumors.
肿瘤细胞分泌的基质降解蛋白酶在肿瘤细胞侵袭和转移中起关键作用。通过明胶酶谱法、反向酶谱法和免疫印迹法检测了7种人妇科癌细胞系的无血清条件培养基中的蛋白酶及其抑制剂。所有三种卵巢腺癌细胞系均分泌尿激酶型纤溶酶原激活剂。其中，一种黏液性囊腺癌细胞系还分泌组织型纤溶酶原激活剂、类纤溶酶和胰蛋白酶原。另一方面，两种卵巢未分化癌细胞系主要分泌明胶酶A或B。一种绒毛膜癌细胞系分泌的多种金属蛋白酶量最高，而源自临床早期的子宫内膜腺癌细胞系（HEC-1）几乎不分泌任何明胶分解酶。这五种高蛋白酶产生者几乎不分泌相应的抑制剂，如金属蛋白酶组织抑制剂（TIMP）-1、-2或纤溶酶原激活剂抑制剂-1。与这些高恶性细胞系相反，低蛋白酶产生者HEC-1分泌大量的TIMP。因此，蛋白水解趋势增强似乎与源自高恶性肿瘤的妇科癌细胞有关。
