Insulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in the plasma of children with Wilms' tumour

doi:10.1016/0959-8049(93)90455-O

European Journal of Cancer

Volume 29, Issue 14, 1993, Pages 1973-1977

https://doi.org/10.1016/0959-8049(93)90455-O Get rights and content

Abstract

Insulin-like growth factors (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) have been measured in plasma of children with Wilms' tumour. The mean levels for total serum IGF-I and -II were not significantly altered in Wilms' tumour as compared with normal control plasma. However, the chromatographic profiles for IGF-I and -II in these groups were different with regard to the presence of IGF binding proteins and high molecular weight forms of IGFs; the high molecular weight form (9–15 kD) of IGF-II was significantly reduced in Wilms' tumour. Levels of IGFBP-2 were substantially elevated in serum from Wilms' tumour patients (1025 ± 112 ng/ml compared with 416 ± 44 ng/ml in controls), and inversely correlated with the levels of high molecular weight forms of IGF-II. We suggest that IGFBP-2 measurements might be of value as a marker for monitoring this type of tumour, either as an adjunct to diagnosis or surveillance of tumour growth during therapy.

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Cited by (45)

Effects of insulin-like growth factors and insulin-like growth factor binding protein-2 on the in vitro proliferation of peripheral blood mononuclear cells
2005, Human Immunology
Increasing evidence has implicated that insulin-like growth factors (IGFs), polypeptides structurally related to proinsulin, are involved in the function and development of the immune system. To probe the relevance of IGF binding protein 2 (IGFBP-2) in T-cell activation and proliferation, we studied the role of IGFBP-2 in anti-CD3 monoclonal antibody (mAb)-activated peripheral blood mononuclear cells (PBMCs). Secretion of IGF-I, IGF-II, and IGFBP-2 by PBMCs from healthy adult donors was determined by radioimmunoassays (RIAs). The PBMC proliferative response after stimulation with anti-CD3 mAb and exposure to increasing concentrations of IGF-I, IGF-II, IGFBP-2, and anti-IGFBP-2 were determined by bromodeoxyuridine enzyme-linked immunosorbent assay. Observations were tested for significance by paired t-tests. We demonstrate an increase in IGFBP-2 secretion associated with both activation of PBMC by anti-CD3 mAb and increasing cell density. Incubation with exogenous IGFBP-2 increased the proliferation of PBMCs, whereas anti-IGFBP-2 had an antiproliferative effect on PBMCs that was reversed by simultaneous exposure to IGFBP-2. The stimulatory activity of IGFBP-2 (1–10 ng/ml) on anti-CD3 mAb-activated PBMCs was similar to that of IGF-I and IGF-II (1–100 ng/ml), with the mean increase in PBMC proliferative response ranging between 150% and 160% for IGFBP-2 (p = 0.03), 150% and 170% for IGF-I (p < 0.01), 133%–161% for IGF-II (p < 0.01), and 157% and 175% for IGF-I + IGF-II (p < 0.01). Thus, our data strongly suggest a role for IGFBP-2 as a local growth factor contributing to the proliferation and activation of mononuclear cells.
Expression of the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) in human gastric cancer cells
2001, European Journal of Cancer
Citation Excerpt :
The ubiquitous expression of IGFBP-2 in the panel of cell lines studied here suggests that IGFBP-2 is intimately associated with the malignant phenotype, and confers some growth advantage on the tumour cells. Several studies have suggested that IGFBP-2 expression may be associated with malignancy [27,28], but the exact role of IGFBP-2 in tumour development including gastric cancer is not known. Based on the finding that the serum level of IGFBP-2 is increased in various types of tumours, Zumkeller and colleagues [28] concluded that the serum IGFBP-2 measurement could be a useful marker for the diagnosis of various malignancies.
Insulin-like growth factor (IGF)-I and -II are potent mitogens and postulated to exert autocrine, and paracrine effects on growth regulation in human gastric cancer. Their mitogenic effects are tightly regulated by the IGF binding proteins (IGFBPs). In this study, we evaluated the mRNA expression of IGF-I, IGF-II and the IGFBPs in a panel of human gastric cancer cell lines, and normal and tumour tissue specimens from patients with gastric cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and competitive PCR. Conditioned media (CM) of the gastric cancer cell lines were studied for the secretion of the IGFBPs by western ligand blot (WLB) and western immunoblot (WIB). IGF-I and IGF-II were expressed in all of the gastric cancer cell lines, and the normal and tumour tissue specimens. Overexpression of the IGFs, in particular, IGF-II, was observed in the tumour tissues. The expression pattern of IGFBPs was heterogeneous among the gastric cancer cell lines. IGFBP-2 was expressed in all of the gastric cancer cell lines, whereas IGFBP-1 was not detected in any cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, IGFBP-5 and IGFBP-6 were expressed in approximately 50% of cell lines. In addition, exogenous IGF-I and IGF-II stimulated the proliferation of gastric cancer cells, suggesting the existence of a functional IGF system in gastric cancer. Taken together, our data-suggest that the IGF-IGFBP system may play an important role in the initiation, progression and metastasis of gastric cancer. Further studies are needed to understand the exact role of IGFs and IGFBPs in gastric neoplasia.
Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted wilms' tumour
2000, Journal of Pediatric Surgery
Citation Excerpt :
If survival rate is to improve for children with poorly responsive, unfavorable histology tumors, then earlier identification is paramount. A number of factors have been identified in the serum and urine of children with WT, including hyaluronic acid—stimulating activity (HASA), hyaluronidase, basic fibroblast growth factor, insulinlike growth factor-2, renin, and erythropoietin.15-20 Although fluctuations in these markers have been associated with the diagnosis, remission, and recurrence of disease, none has proven to be a reliable predictor of tumor stage, invasiveness, histology, nor, more importantly, unfavorable histology findings.
Background/Purpose: The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT. Methods: Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SCID) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined. Results: Sera of mice supporting tumor growth had a median HA concentration of 9,379 μg/L (range, 459 to 3,206,176 μg/L) compared with a median HA concentration of 416 μg/L (range, 204 to 782 μg/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal-predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness. Conclusions: Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness. J Pediatr Surg 35:1070-1078. Copyright © 2000 by W.B. Saunders Company.
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2021, Oncogene
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2020, Oncogene
Analyzing the gene expression profile of anaplastic histology Wilms' tumor with real-time polymerase chain reaction arrays
2015, Cancer Cell International

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PaperInsulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in the plasma of children with Wilms' tumour

Abstract

J Biol Chem

The role of insulin-like growth factors and IGF-binding proteins in the physiological and pathological processes of the kidney

Virchows Archiv B Cell Pathol

Insulin-like growth factors I and II (review)

Eur J Biochem

Pattern of insulin-like growth factor II gene expression during rat embryogenesis

Development

Temporal changes in the expression of the insulin-like growth factor II gene associated with maturation in the human fetus

Development

Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas

Cancer Res

Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycaemia

N Engl J Med

Insulin-like growth factors in human cancer

Expression of insulin-like growth factor-II transcripts in Wilms' tumour

Nature

Insulin-like growth factor II in Wilms' tumors and embryonic tissues

Nature

Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms' tumors: expression at the mRNA and protein level

The regulation of the mRNA of an insulin-like growth factor binding protein (IBP-2) in the rat

Expression, distribution and biological action of insulin-like growth factor binding proteins during development

Expression of the IGFBP-2 gene in post-implantation rat embryos

Development

Paper
Insulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in the plasma of children with Wilms' tumour