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Title: Overexpression of insulin-like growth factor binding protein-6 inhibits rhabdomyosarcoma growth in vivo.
Austin Authors: Gallicchio, M A;Kneen, M;Hall, C;Scott, Andrew M ;Bach, Leon A
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre (Austin Campus) Heidelberg, Victoria, Australia
Issue Date: 1-Dec-2001
Publication information: International Journal of Cancer. Journal International Du Cancer; 94(5): 645-51
Abstract: Rhabdomyosarcoma 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.
Gov't Doc #: 11745458
Journal: International journal of cancer. Journal international du cancer
Type: Journal Article
Subjects: Animals
Cell Division
Insulin-Like Growth Factor Binding Protein 6.physiology
Mice, Inbred BALB C
Mice, Nude
Rhabdomyosarcoma.pathology.prevention & control
Tumor Cells, Cultured
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