Prezas Panagiotis, Arlt Matthias J E, Viktorov Petar, Soosaipillai Antoninus, Holzscheiter Leon, Schmitt Manfred, Talieri Maroulio, Diamandis Eleftherios P, Krüger Achim, Magdolen Viktor
Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, D-81675 Munich, Germany, and G. Papanicolaou Research Center of Oncology, Saint Savas Hospital, GR-11522 Athens, Greece.
Biol Chem. 2006 Jun;387(6):807-11. doi: 10.1515/BC.2006.102.
The human tissue kallikrein family of serine proteases (hK1-hK15 encoded by the genes KLK1-KLK15) is involved in several cancer-related processes. Accumulating evidence suggests that certain tissue kallikreins are part of an enzymatic cascade pathway that is activated in ovarian cancer and other malignant diseases. In the present study, OV-MZ-6 ovarian cancer cells were stably co-transfected with plasmids expressing hK4, hK5, hK6, and hK7. These cells displayed similar proliferative capacity as the vector-transfected control cells (which do not express any of the four tissue kallikreins), but showed significantly increased invasive behavior in an in vitro Matrigel invasion assay (p<0.01; Mann-Whitney U-test). For in vivo analysis, the cancer cells were inoculated into the peritoneum of nude mice. Simultaneous expression of hK4, hK5, hK6, and hK7 resulted in a remarkable 92% mean increase in tumor burden compared to the vector-control cell line. Five out of 14 mice in the 'tissue kallikrein overexpressing' group displayed a tumor/situs ratio greater than 0.198, while this weight limit was not exceeded at all in the vector control group consisting of 13 mice (p=0.017; chi2 test). Our results strongly support the view that tumor-associated overexpression of tissue kallikreins contributes to ovarian cancer progression.
人类丝氨酸蛋白酶组织激肽释放酶家族（由基因KLK1 - KLK15编码的hK1 - hK15）参与多种癌症相关过程。越来越多的证据表明，某些组织激肽释放酶是一种酶促级联途径的一部分，该途径在卵巢癌和其他恶性疾病中被激活。在本研究中，OV - MZ - 6卵巢癌细胞被稳定共转染了表达hK4、hK5、hK6和hK7的质粒。这些细胞与载体转染的对照细胞（不表达四种组织激肽释放酶中的任何一种）表现出相似的增殖能力，但在体外基质胶侵袭试验中显示侵袭行为显著增加（p<0.01；曼 - 惠特尼U检验）。为了进行体内分析，将癌细胞接种到裸鼠的腹膜中。与载体对照细胞系相比，hK4、hK5、hK6和hK7的同时表达导致肿瘤负荷平均显著增加92%。“组织激肽释放酶过表达”组的14只小鼠中有5只的肿瘤/原位比值大于0.198，而在由13只小鼠组成的载体对照组中，没有一只小鼠超过这个重量限制（p = 0.017；卡方检验）。我们的结果有力地支持了以下观点：组织激肽释放酶与肿瘤相关的过表达促进了卵巢癌的进展。
