Bilandzic Maree, Wang Yao, Ahmed Nuzhat, Luwor Rodney B, Zhu Hong Jian, Findlay Jock K, Stenvers Kaye L
MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia.
MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia.
Cancer Lett. 2014 Nov 1;354(1):107-14. doi: 10.1016/j.canlet.2014.07.039. Epub 2014 Aug 13.
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.
转移性卵巢颗粒细胞瘤（GCT）表现出β聚糖缺失。在此，我们检验了这样一个假设，即β聚糖通过抑制NFκB/TGFβ2诱导的基质金属蛋白酶-2（MMP2）来阻断GCT转移。人GCT和人GCT细胞模型显示出显著的MMP2表达，其依赖于NFκB活性，并以NFκB依赖的方式受到TGFβ2的刺激。β聚糖抑制基础和TGFβ2诱导的MMP2表达，并在非贴壁球体培养和体内转移异种移植模型中对抗GCT细胞的转移行为。这些数据表明，在肿瘤细胞首次侵入腹膜时，NFκB/TGFβ2促进GCT转移的早期阶段，而β聚糖则阻碍这一过程。
