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

页码：107 / 114

页数：8

共 39 条

[21] HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts [J].

Ko, Song Yi ;

Barengo, Nicolas ;

Ladanyi, Andras ;

Lee, Ju-Seog ;

Marini, Frank ;

Lengyel, Ernst ;

Naora, Honami .

JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (10) :3603-3617

[22] Induction of matrix metalloproteinase-2 and -9 via Erk1/2-NF-κB pathway in human astroglia infected with Toxoplasma gondii [J].

Lu, Cheng-You ;

Lai, Shih-Chan .

ACTA TROPICA, 2013, 127 (01) :14-20

[23]

Luwor RB, 2001, CANCER RES, V61, P5355

[24] The type III TGF-β receptor regulates epithelial and cancer cell migration through β-arrestin2-mediated activation of Cdc42 [J].

Mythreye, Karthikeyan ;

Blobe, Gerard C. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (20) :8221-8226

[25] Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor [J].

Nishi, Y ;

Yanase, T ;

Mu, YM ;

Oba, K ;

Ichino, I ;

Saito, M ;

Nomura, M ;

Mukasa, C ;

Okabe, T ;

Goto, K ;

Takayanagi, R ;

Kashimura, Y ;

Haji, M ;

Nawata, H .

ENDOCRINOLOGY, 2001, 142 (01) :437-445

[26] Overexpression of phospholipase D enhances matrix metalloproteinase-2 expression and glioma cell invasion via protein kinase C and protein kinase A/NF-κB/Sp1-mediated signaling pathways [J].

Park, Mi Hee ;

Ahn, Bong-Hyun ;

Hong, Yong-Kil ;

Min, Do Sik .

CARCINOGENESIS, 2009, 30 (02) :356-365

[27] Signal transduction - A cellular rescue team [J].

Pomerantz, JL ;

Baltimore, D .

NATURE, 2000, 406 (6791) :26-29

[28] The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression [J].

Qin, Li ;

Liao, Lan ;

Redmond, Aisling ;

Young, Leonie ;

Yuan, Yuhui ;

Chen, Hongwu ;

O'Malley, Bert W. ;

Xu, Jianming .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (19) :5937-5950

[29] Production of endometrial matrix metalloproteinases, but not their tissue inhibitors, is modulated by progesterone withdrawal in an in vitro model for menstruation [J].

Salamonsen, LA ;

Butt, AR ;

Hammond, FR ;

Garcia, S ;

Zhang, J .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (05) :1409-1415

[30] Effects of TGFbeta2 on Wild-Type and Tgfbr3 Knockout Mouse Fetal Testis [J].

Sarraj, Mai A. ;

Escalona, Ruth M. ;

Western, Patrick ;

Findlay, Jock K. ;

Stenvers, Kaye L. .

BIOLOGY OF REPRODUCTION, 2013, 88 (03)

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