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 journalArticleResearchpeer-review

18 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 languageEnglish
Pages (from-to)107 - 114
Number of pages8
JournalCancer Letters
Volume354
Issue number1
DOIs
Publication statusPublished - 2014

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