| Title: |
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 |
| Authors: |
Elmlinger, MW; Sanatani, MS; Bell, M; Dannecker, GE; Ranke, MB |
| Source: |
European Journal of Endocrinology ; page 337-343 ; ISSN 0804-4643 1479-683X |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
1998 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| DOI: |
10.1530/eje.0.1380337 |
| Availability: |
https://doi.org/10.1530/eje.0.1380337; https://eje.bioscientifica.com/view/journals/eje/138/3/337.xml |
| Accession Number: |
edsbas.FF4110ED |
| Database: |
BASE |