Journal article
Betaglycan blocks metastatic behaviors in human granulosa cell tumors by suppressing NFκB-mediated induction of MMP2
M Bilandzic, Y Wang, N Ahmed, RB Luwor, HJ Zhu, JK Findlay, KL Stenvers
Cancer Letters | Published : 2014
Abstract
Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NFκB/TGFβ2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NFκB activity and stimulated by TGFβ2 in an NFκB-dependent manner. Betaglycan suppressed both basal and TGFβ2-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 NFκB/TGFβ2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first inv..
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Awarded by University of Melbourne
Funding Acknowledgements
This work was supported by a NHMRC-Australia Grant (KLS; JKF, 338516); and Fellowship (JKF, 441101) and by the Victorian Government's Operational Infrastructure Support Program. RBL is a recipient of the Melbourne Brain Centre Post-Doctoral Research Fellowship from the University of Melbourne. Study sponsors had no role in this study. PHI Data Audit 13-31.