{"doi":"10.1530/eje.0.1380337","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","abstract":"<jats:p>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 &lt; 0.001) increase in IGFBP-2 secretion and enhanced growth (P &lt; 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.</jats:p>","journal":"European Journal of Endocrinology","year":1998,"id":32725,"datarank":2.226113461253742,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"self_citation_contribution":0.515098080672772,"citation_network_contribution":1.71101538058097,"self_endowment_contribution":0.515098080672772,"citer_contribution":1.71101538058097,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":29,"citers_with_citation_signal":28,"citers_with_endowment":28,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":172687,"name":"MS Sanatani","orcid":null,"position":1,"is_corresponding":false},{"id":172688,"name":"M Bell","orcid":null,"position":2,"is_corresponding":false},{"id":172689,"name":"GE Dannecker","orcid":null,"position":3,"is_corresponding":false},{"id":172690,"name":"MB Ranke","orcid":null,"position":4,"is_corresponding":false},{"id":172686,"name":"MW Elmlinger","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9539310","pmcid":null,"openalex_id":"https://openalex.org/W2105749423","authors":[],"funders":[],"total_grants":0,"fwci":2.9401,"citation_percentile":0.91411043,"influential_citations":4,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2018,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://eje.bioscientifica.com/downloadpdf/journals/eje/138/3/337.pdf","host_type":"journal"},{"url":"https://eje.bioscientifica.com/downloadpdf/journals/eje/138/3/337.pdf","host_type":"BRONZE"},{"url":"https://eje.bioscientifica.com/downloadpdf/journals/eje/138/3/337.pdf","host_type":"publisher"},{"url":"https://eje.bioscientifica.com/view/journals/eje/138/3/337.xml","host_type":"publisher"},{"url":"https://doi.org/10.1530/eje.0.1380337","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9539310","host_type":"repository"}],"fields_of_study":["Growth Hormone and Insulin-like Growth Factors","Hematopoietic Stem Cell Transplantation","Lymphoma Diagnosis and Treatment","Biology","Medicine","Base Sequence","Binding Sites","Binding, Competitive","Cell Division","DNA Primers","Dose-Response Relationship, Drug","Gene Expression Regulation, Neoplastic","Humans","Insulin","Insulin-Like Growth Factor Binding Protein 2","Insulin-Like Growth Factor Binding Protein 4","Insulin-Like Growth Factor I","Insulin-Like Growth Factor II","Polymerase Chain Reaction","RNA, Messenger","Receptor, IGF Type 1","Time Factors","Tumor Cells, Cultured"],"mesh_terms":["Base Sequence","Binding Sites","Binding, Competitive","Cell Division","Dose-Response Relationship, Drug","Humans","Insulin","Insulin-Like Growth Factor I","Insulin-Like Growth Factor II","RNA, Messenger","Time Factors","Tumor Cells, Cultured","Gene Expression Regulation, Neoplastic","Polymerase Chain Reaction","Receptor, IGF Type 1","DNA Primers","Insulin-Like Growth Factor Binding Protein 2","Insulin-Like Growth Factor Binding Protein 4"],"keywords":["Autocrine signalling","Paracrine signalling","Endocrinology","Internal medicine","Insulin-like growth factor 2","Growth factor","Insulin-like growth factor","Insulin-like growth factor-binding protein","Receptor","Biology","Secretion","Cell growth","Medicine","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T14:19:43.332477Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}