Various components of the insulin-like growth factor system in tumor tissue, cerebrospinal fluid and peripheral blood of pediatric medulloblastoma and ependymoma patients
Corresponding Author
Judith M. de Bont
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Fax: +31-10-4089433.
Erasmus MC, Sophia Children's Hospital, Department of Pediatric Oncology and Hematology, sp2456, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The NetherlandsSearch for more papers by this authorJaap van Doorn
Department of Metabolic and Endocrine Diseases and Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for more papers by this authorRoel E. Reddingius
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorGerard H.M. Graat
Department of Metabolic and Endocrine Diseases and Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for more papers by this authorMonique M.C.J. Passier
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorMonique L. den Boer
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorRob Pieters
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Judith M. de Bont
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Fax: +31-10-4089433.
Erasmus MC, Sophia Children's Hospital, Department of Pediatric Oncology and Hematology, sp2456, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The NetherlandsSearch for more papers by this authorJaap van Doorn
Department of Metabolic and Endocrine Diseases and Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for more papers by this authorRoel E. Reddingius
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorGerard H.M. Graat
Department of Metabolic and Endocrine Diseases and Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for more papers by this authorMonique M.C.J. Passier
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorMonique L. den Boer
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorRob Pieters
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
Search for more papers by this authorAbstract
The insulin-like growth factor (IGF) system plays an important role in neuronal development and may contribute to the development of brain tumors. In this study, we studied mRNA expression levels of IGFs, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor receptors (IGFRs) in 27 pediatric medulloblastomas, 13 pediatric ependymomas and 5 control cerebella. Compared to normal cerebellum, mRNA levels of IGFBP-2 and IGFBP-3 were significantly increased in medulloblastomas and ependymomas. IGFBP-2 expression was indicative of poor prognosis in medulloblastomas, whereas IGFBP-3 mRNA levels were especially high in anaplastic ependymomas. IGFBP-5 and IGF-II mRNA levels were significantly increased in ependymomas compared to control cerebellum. Protein expression levels of IGFs and IGFBPs were analyzed in the cerebrospinal fluid (CSF) of 16 medulloblastoma, 4 ependymoma and 23 control patients by radioimmuno assay to determine whether they could be used as markers for residual disease after surgery. No aberrant CSF protein expression levels were found for ependymoma patients. In medulloblastoma patients, the IGFBP-3 protein levels were significantly higher than in ependymoma patients and controls. Moreover, enhanced levels of proteolytic fragments of IGFBP-3 were found in the CSF of medulloblastoma patients, being in concordance with a significantly increased IGFBP-3 proteolytic activity in the CSF of these patients. In conclusion, our data suggest that the IGF system is of importance in pediatric medulloblastomas and ependymomas. Larger studies should be conducted to validate the predictive values of the levels of intact IGFBP-3 and proteolytic fragments in CSF in the follow-up of medulloblastomas. © 2008 Wiley-Liss, Inc.
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