Differential patterns of insulin‐like growth factor‐I and ‐II mRNA expression in medulloblastoma

Abstract

Insulin-like growth factors (IGFs) play an important role in tumour growth and development. We hypothesized that this is also the case for medulloblastomas, which are highly malignant cerebellar brain tumours usually occurring in children. In these tumours the expression patterns of IGF-I and -II mRNA were studied. Tumour specimens obtained from 12 children and two adults at diagnosis were hybridized in situ with digoxigenin-labelled cRNA probes for hIGF-I and hIGF-II mRNAs. In all cases, tumour cells showed abundant expression of IGF-I mRNA. Nine of the 14 tumours showed variable but significant IGF-II expression. In these tumours, the hybridization signal almost exclusively colocalized with a subpopulation of Ki-M1P positive cells that were identified as ramified microglia (RM) cells. In the five tumours without IGF-II expression, microglia/brain macrophages with a more rounded amoeboid-like morphology predominated. RM cells in normal cerebellar tissues, residing abundantly in areas of the white and, to a less extent, in the grey matter, were IGF-II mRNA-negative. These RM cells showed a thinner and more extensively branched appearance and were more evenly distributed than those encountered in medulloblastoma. Probably, during the transformation from the resting ramified towards the amoeboid morphology (or vice versa) IGF-II mRNA expression is only temporarily induced. The physiological meaning of the induction of IGF-II mRNA expression by these cells in medulloblastoma remains unclear but any IGF-II peptide synthesized could exert unfavourable mitogenic and antiapoptotic effects on adjacent tumour cells. However, in this relatively small number of cases we could not find any indications for a relationship between clinical characteristics of the various cases and the extent of IGF-II mRNA expression.

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

“…The IGF system is known to have an important function in the development and growth of the CNS [138] and also appears to play a pivotal role in the development and growth of medulloblastomas and ependymomas [139][140][141][142]. A microarray study identified overexpression of IGF2 by desmoplastic medulloblastomas [143], and similar results were obtained for ependymomas, although not all the samples analyzed were pediatric cases [144].…”

“…A microarray study identified overexpression of IGF2 by desmoplastic medulloblastomas [143], and similar results were obtained for ependymomas, although not all the samples analyzed were pediatric cases [144]. Similarly, abundant expression of IGF1 and IGF2 mRNA was demonstrated in pediatric medulloblastoma tumors [142]. Furthermore, the phosphorylated activated form of IGF1R has been detected in medulloblastoma cell lines and biopsies from pediatric patients [139,140].…”

Insulin-like Growth Factor 2 Is Required for Progression to Advanced Medulloblastoma in patched1 Heterozygous Mice

“…Insulin-like growth factor 2 ( igf2 ) is expressed at high levels compared to normal tissue in both MB and RMS in ptc1 +/- mice (16) and in humans (19, 20, 21, 22). Hahn et al demonstrated that igf2 is critical for the formation of both MB and RMS in ptc1 +/- mice.…”

Various components of the insulin‐like growth factor system in tumor tissue, cerebrospinal fluid and peripheral blood of pediatric medulloblastoma and ependymoma patients

“…The insulin‐like growth factor (IGF) system plays an important role in the regulation of the development and growth of the CNS,3 but also that of medulloblastoma and ependymoma 4–8. This complex system consists of 2 mitogenic and antiapoptotic peptides, IGF‐I and IGF‐II, 2 IGF‐receptors (IGF‐IR and IGF‐IIR), 6 IGF binding proteins (IGFBP1‐6), several IGFBP cell surface receptor proteins and IGFBP proteases 9.…”