Insulin-like growth factor binding protein-4 (IGFBP-4) is a novel anti-angiogenic and anti-tumorigenic mediator secreted by dibutyryl cyclic AMP (dB-cAMP)-differentiated glioblastoma cells.
作者： María J. Moreno , Marguerite Ball , Moises F. Andrade , Angela McDermid , Danica B. Stanimirovic
DOI: 10.1002/GLIA.20345
关键词:
摘要: cAMP has been shown to reverse the transformed phenotype of various cancer cells. Human glioblastoma U87MG cells exposed 500 microM dB-cAMP for 6 days showed reduced proliferation, attenuated invasiveness, and inability induce angiogenic responses in human brain endothelial (HBECs) grown Matrigeltrade mark. VEGF was principal mediator actions conditioned media (CM), since neutralizing antibody completely inhibited U87MG-induced no detectable levels IGF, bFGF, PlGF were found CM. release induced ( approximately 20%) dB-cAMP-treated cells, suggesting a simultaneous induction anti-angiogenic mediators. Down-stream effectors investigated by microarray gene expression analysis. Detected increases differentiation genes, staniocalcin-1 Wnt-5a, angiogenesis-related PAI-1, SPARC, IGFBP-4, IGFBP-7, PAPP-A, PRSS-11 validated real-time PCR, Western blot, and/or ELISA. A subsequent series experiments identified IGFBP-4 as secreted response dB-cAMP. recombinant HBEC CM, whereas anti-human restored pro-angiogenic activity Since neither nor IGF-I, there are known cellular receptors, effect likely IGF-I-independent indirect. also antagonized effects VEGF(165), PlGF, colony formation soft-agar. is novel dB-cAMP-induced anti-tumorigenic that may be promising candidate therapy.
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