Biomaterial Database

Production of insulin-like growth factor-binding proteins by human central nervous system tumors. 1991

T G Unterman, and R P Glick, and G T Waites, and S C Bell

Department of Medicine, University of Illinois College of Medicine, Chicago.

Central nervous system (CNS) tumor cells possess specific receptors for insulin-like growth factors (IGFs) and respond to the growth-promoting effects of IGFs in cell culture. In the present study, we asked whether CNS tumors also produce IGF-binding proteins (BPs) which may modulate the effects of IGFs on CNS tumor cells. Primary cell cultures were established from 20 CNS tumors. Dot blot analysis with 125I-labeled recombinant human IGF-I revealed IGF-binding activity in serum-free conditioned medium from 5 of 7 meningiomas, 7 of 8 malignant gliomas, and 3 of 5 other CNS tumors. Specific IGF BPs in conditioned medium were characterized further by Western ligand and immunoblotting, affinity labeling, and precipitation with specific antibodies against human IGFBP-1, -2, and -3. All conditioned media tested contained an Mr 35,000 BP which was recognized by antiserum against IGFBP-2 and an Mr 24,000 BP that was not recognized by available antisera. Medium conditioned by meningiomas (and one glioma) also contained Mr 45,000 and 50,000 IGF BPs, similar in size and/or immunological properties to growth hormone-dependent BPs present in normal human serum (IGFBP-3). Ligand blotting also showed that meningiomas produce an Mr 29,000 BP; immunoblotting and immunoprecipitation of affinity-labeled IGF-BP complexes confirmed that this BP is recognized by antiserum against IGFBP-1. Immunohistochemistry with specific monoclonal antibodies demonstrated that IGFBP-1 is abundant in pathological specimens of meningiomas and that lower amounts also are detected in malignant gliomas. We conclude that human CNS tumor cells produce a variety of IGF BPs in cell culture, including several that are similar in size and immunological properties to previously characterized human IGF BPs. Immunohistochemistry with specific monoclonal antibodies against IGFBP-1 confirms that this BP is present in vivo, further supporting the concept that IGF BPs may contribute to the regulation of growth in human CNS tumors.

UI	MeSH Term	Description	Entries
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D009363	Neoplasm Proteins	Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.	Proteins, Neoplasm
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015153	Blotting, Western	Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.	Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D018969	Insulin-Like Growth Factor Binding Proteins	A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)	IGF Binding Protein,IGF-Binding Protein,IGF-Binding Proteins,IGFBP,Insulin-Like Growth Factor Binding Protein,Somatomedin-Binding Protein,Somatomedin-Binding Proteins,Binding Protein, IGF,IGF Binding Proteins,Insulin Like Growth Factor Binding Protein,Protein, IGF Binding,Protein, IGF-Binding,Protein, Somatomedin-Binding,Somatomedin Binding Protein,Somatomedin Binding Proteins