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

Cancer Lett. 2014 Nov 1;354(1):107-14. doi: 10.1016/j.canlet.2014.07.039. Epub 2014 Aug 13.

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 invade the peritoneum.

Keywords: Betaglycan; Invasion; Ovarian cancer; Spheroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling
  • Granulosa Cell Tumor / metabolism*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Ovarian Neoplasms / metabolism*
  • Peritoneum / metabolism
  • Proteoglycans / chemistry*
  • Receptors, Transforming Growth Factor beta / chemistry*
  • Transforming Growth Factor beta2 / metabolism

Substances

  • NF-kappa B
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • betaglycan
  • Matrix Metalloproteinase 2