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Endocrinology Vol. 142, No. 4 1652-1658
Copyright © 2001 by The Endocrine Society

ARTICLES

In Vivo Expression of Insulin-Like Growth Factor-Binding Protein-2 in Human Gliomas Increases with the Tumor Grade1

Martin W. Elmlinger, Martin H. Deininger, Burkhardt S. Schuett, Richard Meyermann, Frank Duffner, Ernst H. Grote and Michael B. Ranke

Pediatric Endocrinology, Children’s Hospital (M.W.E., M.B.R., B.S.S.), Institute of Brain Research (M.H.D., R.M.), and Department of Neurosurgery (F.D., E.H.G.), University of Tuebingen, D-72076 Tuebingen, Germany

Address all correspondence and requests for reprints to: Dr. Martin W. Elmlinger, Section of Pediatric Endocrinology, Children’s Hospital, University of Tuebingen, Hoppe-Seyler Strasse 1, D-72076 Tuebingen, Germany. E-mail: martin.elmlinger{at}med.uni-tuebingen.de

Human central nervous system tumors and glioma cell lines highly express the insulin-like growth factor-binding protein (IGFBP)-2. As IGFBP-2 can affect tumor growth, we studied the relationship between IGFBP-2 expression and the malignancy of brain tumors in vivo. To do so, we investigated by immunohistochemistry the accumulation of IGFBP-1, -2, and -3 in 50 human gliomas classified by the WHO Malignancy Scale. Double labeling using anti-CD68 (monocytes/macrophages), antiglial fibrillary acidic protein, and anti-CD3 (T cells) antibodies was performed to further characterize the IGFBP-1, -2, and -3+ cells. The expression of IGFBP messenger RNAs (mRNAs) was tested by RT-PCR in tumor samples from nine gliomas of different grades and in eight cell lines representing the cellular composition of human glioma. As controls, the accumulation of IGFBP-2 was investigated in normal brain and in the rat C6 glioblastoma model. IGFBP-1 and -3 accumulated in endothelial and macrophage/microglial cells. IGFBP-2+ macrophage/microglial and glioma cells clustered in the immediate vicinity of focal necrosis of the human gliomas as well as of the rat C6 glioblastoma. The labeling score of IGFBP-1 accumulation in endothelial cells correlated negatively (P = 0.0229), and that of IGFBP-2 accumulation in glioma cells correlated positively (P < 0.0006) with the tumor grade of the gliomas. In addition, RT-PCR analysis confirmed mRNA expression of IGFBP-1, -2, and -3 by the gliomas and glial cells. Small amounts of IGFBP-1 and -3 mRNA, but high amounts of IGFBP-2 mRNA, were detectable in macrophage-like and glioma cell lines.

The results suggest cell type-specific accumulation of IGFBP-1, -2, and -3 in human glial tumors of the brain. The increase in IGFBP-2 expression with this malignancy suggests a role of IGFBP-2 in the biology of human gliomas.




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