沃特曼宁
分泌物
CD44细胞
生物
激酶
蛋白激酶A
细胞生物学
信号转导
细胞培养
分子生物学
A549电池
癌症研究
磷脂酰肌醇
细胞
内分泌学
生物化学
遗传学
作者
Yanying Zhang,Aye Aye Thant,Kazuya Machida,Yasukatsu Ichigotani,Yuko Naito,Yukiko Hiraiwa,Takeshi Senga,Yasuyoshi Sohara,Satoru Matsuda,Michinari Hamaguchi
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2002-07-15
卷期号:62 (14): 3962-5
被引量:27
摘要
We investigated the production of matrix metalloproteinase (MMP) by hyaluronan(HA) stimulation in a human cancer cell line, QG90, that expresses a large amount of CD44s, a HA receptor. Treatment of QG90 with HA strongly activated MMP-2 secretion in a time- and dose-dependent manner. We found that expression of antisense CD44s in QG90 cells substantially inhibited the HA-dependent secretion of MMP-2, whereas overexpression of full-length CD44s augmented the HA-dependent secretion of MMP-2. In addition, pretreatment of cells with the neutralizing anti-CD44 antibody significantly inhibited both the HA-dependent MMP-2 secretion and the HA-dependent activation of mitogen-activated protein kinase in a dose-dependent manner. Similarly, treatment of cells with a Ras farnesyltransferase inhibitor, manumycin A, strongly inhibited the HA-dependent MMP-2 secretion. Moreover, in vitro invasiveness of QG90 and its activation by HA were clearly suppressed by the expression of antisense CD44s. In addition, treatment of cells with anti-CD44, a mitogen-activated protein/extracellular signal-regulated kinase kinase 1 inhibitor, PD98059, or phosphatidylinositol 3'-kinase inhibitors, wortmannin and LY294002, effectively blocked the HA-dependent activation of the invasiveness. In contrast, overexpression of full-length CD44 substantially activated the invasiveness of QG90. Taken together, HA-CD44s signaling plays a key role in the HA-dependent secretion of MMP-2 and, hence, in the invasiveness of QG90 cells.
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