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Glioblastoma multiforme is a diffusely infiltrating primary neoplasm of glial origin. Its uniformly fatal prognosis has not changed appreciably over the past decade, and the only modifiable factor associated with survival is the extent of surgical resection. In the absence of a concomitant lesion that is likely to change local treatment, the factors that predict disease recurrence include extensive tumor involvement of white matter tracts and the pattern of invasion of the neuropil. The molecular pathogenesis of glioblastoma is uncertain, but recent advances in understanding the genetic alterations in this tumor and the relationships between these molecular changes and the biologic behavior of the tumor provide a basis for designing therapeutic strategies that will improve long-term survival.Regulation of growth-related signaling events in PC12 cells by the rat homolog of the mouse insulin-like growth factor binding protein, IGFBP-3.
IGFBP-3 is a secreted protein produced by most non-tumorigenic cell types and is homologous to the mouse insulin-like growth factor binding protein 2. The IGFBP-3 is secreted by many of the same cell types as the insulin-like growth factor 2 (IGF2) and is transported by the circulation to the cell surface where it can either directly or indirectly bind and modulate the activity of these growth factors. Using PC12 cells, we examined the effects of IGFBP-3 on the mitogen-activated phosphorylation of the IGF2 receptor and the activation of MAP kinase in these cells. IGFBP-3 inhibited IGF2-stimulated phosphorylation of the IGF2 receptor and MAP kinase activation. The secreted protein was found in conditioned media of PC12 cells grown in serum-free medium but, unlike the IGF2, was not detectable in the medium of serum-supplemented cells. The IGFBP-3 was protease sensitive and its biological activity was lost after endoproteinase Arg-C