INSULIN-LIKE GROWTH-FACTORS (IGF) ENHANCE 3-DIMENSIONAL (3D) GROWTH OF HUMAN GLIOBLASTOMAS

Human glioblastomas (gliomas) are characterized as rapidly growing bra in tumors which are highly invasive but rarely metastatic, Human gliom as synthesize and secrete increased levels of insulin-like growth fact ors (IGFs) as well as expressing increased numbers of IGF receptors wh en compared to normal brain tissue. These observations suggest the exi stence of an IGF-mediated autocrine mechanism for glioma growth regula tion. The purpose of this study was to examine the effect of human rec ombinant IGF (hrIGF) treatment on the in vitro growth of human glioma monolayer and three-dimensional (3D) multicellular spheroid cultures. The data demonstrate that hrIGF-I treatment of glioma cell lines sligh tly enhanced tumor monolayer proliferation as measured by [H-3]thymidi ne incorporation.-In contrast, treatment of glioma spheroids with hrIG F-I or hrDes(1-3)IGF-I, the truncated brain form of IGF-I, dramaticall y enhanced 3D tumor growth with a 1.5-2-fold reduction in spheroid dou bling time (FRSDT), In addition, IGF-treated glioma spheroids were mor e densely packed than spheroids grown in media alone with no observed necrosis. These data suggest that IGFs will dramatically enhance gliom a proliferation when 3D cell-cell contact occurs, This observed enhanc ement suggests that IGFs both synthesized in the brain and systemicall y support rapid proliferation of gliomas in vivo. (C) 1997 Elsevier Sc ience Ireland Ltd.