Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4 expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action but not by IGF type I receptor expression

We recently found evidence indicating that the source of elevated serum insulin-like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T-cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and growth of leukemic cells through the IGF type I receptor. We m...

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Bibliographic Details
Published in:European journal of endocrinology 1998-03, Vol.138 (3), p.337-343
Main Authors: ELMLINGER, M. W, SANATANI, M. S, BELL, M, DANNECKER, G. E, RANKE, M. B
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites
Binding, Competitive
Biological and medical sciences
Cell Division - drug effects
Cell Division - physiology
DNA Primers - chemistry
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - genetics
Hematologic and hematopoietic diseases
Humans
Insulin - pharmacology
Insulin-Like Growth Factor Binding Protein 2 - analysis
Insulin-Like Growth Factor Binding Protein 2 - biosynthesis
Insulin-Like Growth Factor Binding Protein 2 - genetics
Insulin-Like Growth Factor Binding Protein 4 - analysis
Insulin-Like Growth Factor Binding Protein 4 - biosynthesis
Insulin-Like Growth Factor Binding Protein 4 - genetics
Insulin-Like Growth Factor I - analogs & derivatives
Insulin-Like Growth Factor I - pharmacology
Insulin-Like Growth Factor II - pharmacology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Polymerase Chain Reaction
Receptor, IGF Type 1 - analysis
Receptor, IGF Type 1 - drug effects
Receptor, IGF Type 1 - genetics
RNA, Messenger - analysis
RNA, Messenger - genetics
Time Factors
Tumor Cells, Cultured
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Summary:We recently found evidence indicating that the source of elevated serum insulin-like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T-cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and growth of leukemic cells through the IGF type I receptor. We measured IGFBP-2, -4 and IGF type I receptor (IGF-I-R) mRNA by RT-PCR, cell growth and IGFBP-2 secretion (per 10(6) cells). IGF-I-R binding sites were assessed by 125I-IGF replacement studies. Inhibition using an IGF-II antibody showed that tumor cell-derived IGF-II accounts for a significant 25% (P < 0.001) increase in IGFBP-2 secretion and enhanced growth (P < 0.01) of leukemic T-cells after 7 days in culture. IGFBP-2 secretion, but not IGFBP-2 mRNA was specifically increased by IGFs, while no specific effect of insulin was detectable. The addition of 100 ng/ml IGF-II enhanced the IGFBP-2 secretion 2.8-fold, while the use of IGF-I only enhanced IGFBP-2 secretion 1.7-fold, although IGF-I enhanced IGF-II action. Through inhibition using JB1, a peptide inhibiting the IGF signal transduction by blocking the IGF-I-R, we demonstrated the involvement of the IGF-I-R in IGFBP-2 and -4 expression and leukemic cell growth. However, only slight differences in the IGF-I-R mRNA expression were seen for T- and B-cells compared with the differences found for the IGFBP-2 and -4 mRNA or IGFBP-2 secretion. Thus, although IGF-I-R mediates the autocrine/paracrine effects of the IGFs, IGF-I-R mRNA expression is most probably not involved in the differential IGFBP-2/IGFBP-4 expression in leukemic cells.
ISSN:0804-4643
1479-683X
DOI:10.1530/eje.0.1380337