Biomaterial Database

Divergent responses of human astrocytoma and non-neoplastic astrocytes to tumor necrosis factor alpha involve the 55 kDa tumor necrosis factor receptor. 1993

B P Barna, and G H Barnett, and B S Jacobs, and M L Estes

Department of Clinical Pathology, Cleveland Clinic Foundation, OH 44195-5131.

The effects of tumor necrosis factor (TNF) on DNA synthesis, proliferation, and induction of gene/protein expression of TNF were compared in neoplastic and non-neoplastic adult human astrocytes. Previously, we demonstrated that TNF induced proliferative responses in non-neoplastic adult human astrocytes. In astrocytoma cells, however, TNF elicited both proliferative and cytostatic responses depending upon cell density and TNF concentration. This bimodal effect persisted even in a homogeneous, cloned astrocytoma cell line (STT-9C), and was inhibitable by neutralizing antibody to TNF. TNF treatment enhanced expression of TNF mRNA in astrocytoma cells but not in non-neoplastic astrocytes, and cell-associated or secreted TNF was detectable in any culture. The involvement of receptors in astrocyte responses to TNF was examined in serological studies using monoclonal antibodies Utr-1 to the 75 kDa, and Htr-9 to the 55 kDa TNF receptor. Antibody to the 55 kDa TNF receptor alone was able to mimic the effects of TNF in both neoplastic and non-neoplastic astrocyte cultures while antibody to the 75 kDa TNF receptor had no effect. These data indicate that the bimodal actions of TNF on human astrocytoma cells as well as the stimulatory effects on non-neoplastic adult astrocytes are regulated at least in part by the 55 kDa TNF receptor. Astrocyte TNF receptors, however, do not appear to constitute part of an autocrine growth pathway in either non-neoplastic or neoplastic human astrocytes.

UI	MeSH Term	Description	Entries
D009447	Neuroblastoma	A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	Neuroblastomas
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001253	Astrocytes	A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.	Astroglia,Astroglia Cells,Astroglial Cells,Astrocyte,Astroglia Cell,Astroglial Cell,Astroglias,Cell, Astroglia,Cell, Astroglial
D001254	Astrocytoma	Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)	Astrocytoma, Subependymal Giant Cell,Glioma, Astrocytic,Oligoastrocytoma, Mixed,Pleomorphic Xanthoastrocytomas,Anaplastic Astrocytoma,Astrocytoma, Grade I,Astrocytoma, Grade II,Astrocytoma, Grade III,Astrocytoma, Protoplasmic,Astroglioma,Cerebral Astrocytoma,Childhood Cerebral Astrocytoma,Fibrillary Astrocytoma,Gemistocytic Astrocytoma,Intracranial Astrocytoma,Juvenile Pilocytic Astrocytoma,Pilocytic Astrocytoma,Subependymal Giant Cell Astrocytoma,Anaplastic Astrocytomas,Astrocytic Glioma,Astrocytic Gliomas,Astrocytoma, Anaplastic,Astrocytoma, Cerebral,Astrocytoma, Childhood Cerebral,Astrocytoma, Fibrillary,Astrocytoma, Gemistocytic,Astrocytoma, Intracranial,Astrocytoma, Juvenile Pilocytic,Astrocytoma, Pilocytic,Astrocytomas,Astrocytomas, Grade III,Astrogliomas,Cerebral Astrocytoma, Childhood,Cerebral Astrocytomas,Childhood Cerebral Astrocytomas,Fibrillary Astrocytomas,Gemistocytic Astrocytomas,Gliomas, Astrocytic,Grade I Astrocytoma,Grade I Astrocytomas,Grade II Astrocytoma,Grade II Astrocytomas,Grade III Astrocytoma,Grade III Astrocytomas,Intracranial Astrocytomas,Juvenile Pilocytic Astrocytomas,Mixed Oligoastrocytoma,Mixed Oligoastrocytomas,Pilocytic Astrocytoma, Juvenile,Pilocytic Astrocytomas,Pleomorphic Xanthoastrocytoma,Protoplasmic Astrocytoma,Protoplasmic Astrocytomas,Xanthoastrocytoma, Pleomorphic
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha