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

Maree Bilandzic; Yao Wang; Nuzhat Ahmed; Rodney B Luwor; Hong-Jian Zhu; John (Jock) K Findlay; Kaye L Stenvers

doi:10.1016/j.canlet.2014.07.039

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

Maree Bilandzic, Yao Wang, Nuzhat Ahmed, Rodney B Luwor, Hong-Jian Zhu, John (Jock) K Findlay, Kaye L Stenvers

Research output: Contribution to journal › Article › Research › peer-review

19 Citations (Scopus)

Abstract

Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NFkappaB/TGFbeta2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NFkappaB activity and stimulated by TGFbeta2 in an NFkappaB-dependent manner. Betaglycan suppressed both basal and TGFbeta2-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 NFkappaB/TGFbeta2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first invade the peritoneum.

Original language	English
Pages (from-to)	107 - 114
Number of pages	8
Journal	Cancer Letters
Volume	354
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2014.07.039
Publication status	Published - 2014

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10.1016/j.canlet.2014.07.039

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title = "Betaglycan blocks metastatic behaviors in human granulosa cell tumors by suppressing NF?B-mediated induction of MMP2",

abstract = "Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NFkappaB/TGFbeta2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NFkappaB activity and stimulated by TGFbeta2 in an NFkappaB-dependent manner. Betaglycan suppressed both basal and TGFbeta2-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 NFkappaB/TGFbeta2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first invade the peritoneum.",

author = "Maree Bilandzic and Yao Wang and Nuzhat Ahmed and Luwor, \{Rodney B\} and Hong-Jian Zhu and Findlay, \{John (Jock) K\} and Stenvers, \{Kaye L\}",

year = "2014",

doi = "10.1016/j.canlet.2014.07.039",

language = "English",

volume = "354",

pages = "107 -- 114",

journal = "Cancer Letters",

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TY - JOUR

T1 - Betaglycan blocks metastatic behaviors in human granulosa cell tumors by suppressing NF?B-mediated induction of MMP2

AU - Bilandzic, Maree

AU - Wang, Yao

AU - Ahmed, Nuzhat

AU - Luwor, Rodney B

AU - Zhu, Hong-Jian

AU - Findlay, John (Jock) K

AU - Stenvers, Kaye L

PY - 2014

Y1 - 2014

N2 - Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NFkappaB/TGFbeta2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NFkappaB activity and stimulated by TGFbeta2 in an NFkappaB-dependent manner. Betaglycan suppressed both basal and TGFbeta2-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 NFkappaB/TGFbeta2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first invade the peritoneum.

AB - Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NFkappaB/TGFbeta2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NFkappaB activity and stimulated by TGFbeta2 in an NFkappaB-dependent manner. Betaglycan suppressed both basal and TGFbeta2-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 NFkappaB/TGFbeta2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first invade the peritoneum.

UR - http://www.sciencedirect.com/science/article/pii/S0304383514004182

U2 - 10.1016/j.canlet.2014.07.039

DO - 10.1016/j.canlet.2014.07.039

M3 - Article

SN - 0304-3835

VL - 354

SP - 107

EP - 114

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

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

Abstract

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