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dc.contributor.authorGallicchio, M Aen
dc.contributor.authorKneen, Men
dc.contributor.authorHall, Cen
dc.contributor.authorScott, Andrew Men
dc.contributor.authorBach, Leon Aen
dc.identifier.citationInternational Journal of Cancer. Journal International Du Cancer; 94(5): 645-51en
dc.description.abstractRhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Rhabdomyosarcoma cell lines overexpress insulin-like growth factor-II (IGF-II), an autocrine growth factor that is inhibited by insulin-like growth factor binding protein-6 (IGFBP-6). IGFBP-6 is associated with myoblast quiescence, and expression in rhabdomyosarcoma cells is low. The effect of IGFBP-6 on 2 rhabdomyosarcoma cell lines, RD and Rh30, was studied. IGFBP-6 inhibited anchorage-dependent growth of RD and Rh30 cells in a dose-dependent manner (p < 0.0001). IGFBP-6 also inhibited anchorage-independent growth of RD cells in soft agar in a dose-dependent manner (p < 0.01). Anchorage-independent growth of RD cells on polyhydroxyethylmethacrylate-coated plates was decreased to a minimum of 48% of control after treatment with IGFBP-6 (p < 0.001). In this system, IGFBP-6 increased apoptosis 4-fold (p < 0.001). IGF-II partially reversed the IGFBP-6-induced decrease in growth and increase in apoptosis. Rh30 cells were stably transfected with an IGFBP-6 cDNA and subcutaneous xenografts established in BALB/c nude mice. After 18 days, sizes of 2 independent clones of IGFBP-6-overexpressing Rh30 cells were reduced to 12% and 26% of vector control-transfected tumors (p = 0.0006 and 0.002, respectively). IGFBP-6 therefore inhibits proliferation and promotes apoptosis of rhabdomyosarcoma in vitro and dramatically inhibits xenograft growth in vivo, at least in part by inhibiting IGF-II. Low expression of IGFBP-6 may therefore contribute to rhabdomyosarcoma growth and metastasis.en
dc.subject.otherCell Divisionen
dc.subject.otherInsulin-Like Growth Factor Binding Protein 6.physiologyen
dc.subject.otherMice, Inbred BALB Cen
dc.subject.otherMice, Nudeen
dc.subject.otherRhabdomyosarcoma.pathology.prevention & controlen
dc.subject.otherTumor Cells, Cultureden
dc.titleOverexpression of insulin-like growth factor binding protein-6 inhibits rhabdomyosarcoma growth in vivo.en
dc.typeJournal Articleen
dc.identifier.journaltitleInternational journal of cancer. Journal international du canceren
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin and Repatriation Medical Centre (Austin Campus) Heidelberg, Victoria, Australiaen
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext- Imaging and Therapy- Newton-John Cancer Research Institute-
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