Biomaterial Database

Human neuroblastoma cells use either insulin-like growth factor-I or insulin-like growth factor-II in an autocrine pathway via the IGF-I receptor: variability of IGF, IGF binding protein (IGFBP) and IGF receptor gene expression and IGF and IGFBP secretion in human neuroblastoma cells in relation to cellular proliferation. 1997

W Kiess, and G Koepf, and H Christiansen, and W F Blum

Children's Hospital, Justus Liebig University of Giessen, Germany. wieland.kiess@paediat.med.uni-giessen.de

Neuroblastoma cells are thought to depend upon autocrine stimulation by IGF-II but not by IGF-I. We have studied the expression of IGF, IGFBP and IGF receptor mRNA in two human neuroblastoma cell lines, SK-N-MC and CHP, and asked whether or not the expression of the IGF system in these malignant cells determines their growth pattern. SK-N-MC cells grow with a cell doubling time of 36 hours in medium supplemented with 10% fetal calf serum whereas CHP cells only grow with a doubling time of 72 h. In addition, the SK-N-MC cell line has a plating efficiency ten times greater than the CHP cell line. RNase protection assays were performed using (32)P-labelled riboprobes and RNA that had been purified from SK-N-MC and CHP cells respectively. A 520 bases human IGF-I, a 556 bases human IGF-II, a 480 bases human IGF-I receptor and a 250 human IGF-II/mannose-6-phosphate (M6P) receptor probe were radiolabelled as were human IGFBP-1, -2, -3, -4, -5 and -6 probes. While both SKNMC and CHP neuroblastoma cells expressed mRNAs for IGFBP-2, -4, and -6 no signal was detected for IGFBP-1, and -3 and only SK-N-MC cells expressed IGFBP-5 mRNA. In addition, a 400 bases protected band was seen with the IGF-I receptor probe and a 260 bases protected band with the IGF-IIM6P receptor probe in either cell line. Interestingly, a 300 bases protected species was detected with the IGF-II probe in CHP cell RNA whereas SK-N-MC cells did not express IGF-II transcripts. Conversely, SK-N-MC cells expressed a 520 bases IGF-I transcript while CHP cells did not show IGF-I mRNA expression. As determined by specific radioimmunoassays SK-N-MC cells secreted 0.75+/-0.02 ng/ml IGF-I, 1.2+/-0.04 ng/ml IGF-II and 149+/-2.1 ng/ml IGFBP-2 within 24 h, whereas CHP cells secreted 0.1+/-0.01 ng/ml IGF-I, but 6.2+/-0.1ng/ml IGF-II and 254.8+/-5.5 ng/ml IGFBP-2 (N=5). IGFBP-2 secretion correlated positively with IGF-II secretion in CHP cells (r=0.85, P=0.05) and negatively with IGF-I (r= -0.9, P<0.01) in SK-N-MC cells. In conclusion, SK-N-MC cells which grow rapidly and have a high plating efficiency, express IGF-I, while CHP cells that grow more slowly express IGF-II. We hypothesize that neuroblastoma cells depend upon autocrine stimulation by either IGF-I or IGF-II. Variable sensitivity to growth inhibitors or apoptotic processes may be related to the differential expression of the IGF system.

UI	MeSH Term	Description	Entries
D007334	Insulin-Like Growth Factor I	A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.	IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D007335	Insulin-Like Growth Factor II	A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.	IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
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
D011863	Radioimmunoassay	Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.	Radioimmunoassays
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
D004591	Electrophoresis, Polyacrylamide Gel	Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.	Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012260	Ribonucleases	Enzymes that catalyze the hydrolysis of ester bonds within RNA. EC 3.1.-.	Nucleases, RNA,RNase,Acid Ribonuclease,Alkaline Ribonuclease,Ribonuclease,RNA Nucleases,Ribonuclease, Acid,Ribonuclease, Alkaline
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured