title: Betaglycan blocks metastatic behaviors in human granulosa cell tumors by suppressing NFκB-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 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.
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia. Electronic address: maree.bilandzic@mimr-phi.org.
authors.forename: Maree
authors.initials: M
authors.lastname: Bilandzic
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia; Women's Cancer Research Centre, Royal Women's Hospital, Parkville, Vic. 3052, Australia; Department of Obstetrics and Gynaecology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic. 3052, Australia.
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic. 3052, Australia.
authors.forename: Rodney B
authors.initials: RB
authors.lastname: Luwor
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic. 3052, Australia.
authors.forename: Hong Jian
authors.initials: HJ
authors.lastname: Zhu
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia; Women's Cancer Research Centre, Royal Women's Hospital, Parkville, Vic. 3052, Australia; Department of Obstetrics and Gynaecology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic. 3052, Australia.
authors.forename: Jock K
authors.initials: JK
authors.lastname: Findlay
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia; Department of Developmental Biology and Anatomy, Monash University, Clayton, Vic. 3168, Australia.
authors.forename: Kaye L
authors.initials: KL
authors.lastname: Stenvers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006106:Granulosa Cell Tumor / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010537:Peritoneum / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry*; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; C071736:betaglycan; D020778:Matrix Metalloproteinase 2
keywords: Betaglycan; Invasion; Ovarian cancer; Spheroid