Tsui Ke-Hung, Chang Phei-Lang, Feng Tsui-Hsia, Chung Li-Chuan, Sung Hsin-Ching, Juang Horng-Heng
Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
Anticancer Res. 2008 Jul-Aug;28(4A):1993-9.
Previous studies have identified a subclone cell line (PC-J) which was isolated from a metastatic human prostate cell line, PC-3. In vitro matrigel invasion assays and xenograft animal studies suggested that matriptase was a putative metastatic gene in human prostate carcinoma cells. Although low metastatic prostate tumor cells, LNCaP, also expressed high levels of matriptase mRNA, gelatin zymography indicated that LNCaP cells had extremely low matriptase activity. Further studies using RT-PCR and lectin blotting assays revealed that the expression of N-acetylglucosaminyltransferase V (MGAT5), a glycoprotein that stabilizes matriptase, was low in LNCaP cells compared to PC-3 and PC-J cells. The transient overexpression of MGAT5 significantly enhanced the activity of matriptase and the invasion ability in the LNCaP cells. Knock-down of MGAT5 in PC-3 cells attenuated the metastatic ability of the cells, as determined by the in vitro invasion assay and the xenograft animal studies. Matriptase and MGAT5 may play important role in the metastasis of prostate cancer.
先前的研究已鉴定出一种亚克隆细胞系（PC-J），它是从转移性人前列腺癌细胞系PC-3中分离出来的。体外基质胶侵袭试验和异种移植动物研究表明，膜型丝氨酸蛋白酶是人类前列腺癌细胞中的一个假定转移基因。尽管低转移性前列腺肿瘤细胞LNCaP也表达高水平的膜型丝氨酸蛋白酶mRNA，但明胶酶谱分析表明LNCaP细胞的膜型丝氨酸蛋白酶活性极低。使用逆转录聚合酶链反应（RT-PCR）和凝集素印迹分析的进一步研究显示，与PC-3和PC-J细胞相比，LNCaP细胞中一种稳定膜型丝氨酸蛋白酶的糖蛋白N-乙酰葡糖胺转移酶V（MGAT5）的表达较低。MGAT5的瞬时过表达显著增强了LNCaP细胞中膜型丝氨酸蛋白酶的活性和侵袭能力。通过体外侵袭试验和异种移植动物研究确定，PC-3细胞中MGAT5的敲低减弱了细胞的转移能力。膜型丝氨酸蛋白酶和MGAT5可能在前列腺癌转移中起重要作用。
