Betaglycan blocks metastatic behaviors in human granulosa cell tumors by suppressing NFκB-mediated induction of MMP2

被引：20
作者：
Bilandzic, Maree [1 ]
Wang, Yao [1 ]
Ahmed, Nuzhat [1 ,2 ,3 ]
Luwor, Rodney B. [4 ]
Zhu, Hong Jian [4 ]
Findlay, Jock K. [1 ,2 ,3 ]
Stenvers, Kaye L. [1 ,5 ]
机构：
[1] MIMR PHI Inst Med Res, Clayton, Vic 3168, Australia
[2] Royal Hosp Women, Womens Canc Res Ctr, Parkville, Vic 3052, Australia
[3] Univ Melbourne, Royal Melbourne Hosp, Dept Obstet & Gynaecol, Parkville, Vic 3052, Australia
[4] Univ Melbourne, Royal Melbourne Hosp, Dept Surg, Parkville, Vic 3052, Australia
[5] Monash Univ, Dept Dev Biol & Anat, Clayton, Vic 3168, Australia
来源：
CANCER LETTERS | 2014年 / 354卷 / 01期
基金：
澳大利亚国家健康与医学研究理事会;
关键词：
Betaglycan; Ovarian cancer; Spheroid; Invasion; OVARIAN FOLLICULAR DEVELOPMENT; IN-VITRO; TGF-BETA; MATRIX METALLOPROTEINASE-2; EXTRACELLULAR-MATRIX; CANCER; EXPRESSION; ACTIVATION; CARCINOMA; RECEPTOR;
D O I：
10.1016/j.canlet.2014.07.039
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NF kappa B/TGF beta 2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NF kappa B activity and stimulated by TGF beta 2 in an NF kappa B-dependent manner. Betaglycan suppressed both basal and TGF beta 2-induced MMP2 expression and countered metastatic behaviors of GCT cells in non-adherent spheroid culture and in vivo xenograft models of metastasis. These data suggest that NF kappa B/TGF beta 2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first invade the peritoneum. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：107 / 114
页数：8
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