Do insulin-like growth factor associated proteins qualify as a tumor marker? Results of a prospective study in 163 cancer patients

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective

Insulin-like growth factor (IGF)-1, -2 and Insulin like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated, if the IGF-system can serve as a tumor marker in neoplasms.

Methods

In our prospective study 163 patients with colorectal cancer (22), prostate cancer (21), head and neck tumors (17), lymphomas (20), lung cancer (34) and other entities (49) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared to 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared.

Results

The serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected.

Conclusion

The IGF-system cannot serve as a new tumor marker. The detected differences are very small, sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations.

W H Daughaday, P Rotwein (1989)

There is currently widespread interest in the IGFs (IGF-I and IGF-II) and their roles in the regulation of growth and differentiation of an ever increasing number of tissues are being reported. This selective review focused on the current state of our knowledge about the structure of mammalian IGFs and the multiple forms of mRNAs which arise from alternative splicing and promoter sites which arise from gene transcription. Current progress in the immunological measurement of the IGF is reviewed including different strategies for avoiding binding protein interference. The results of measurements of serum IGF-I and IGF-II in fetus and mother and at various stages of postnatal life are described. Existing knowledge of the concentration of these peptides in body fluids and tissues are considered. Last, an attempt is made to indicate circumstances in which the IGFs are exerting their actions in an autocrine/paracrine mode and when endocrine actions predominate. In the latter context it was concluded that an important role for GH action on skeletal tissues via hepatic production of IGF-I and endocrine action of IGF-I on growth cartilage is likely.

0 comments Cited 121 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin.

E Rinderknecht, R Humbel (1978)

The complete amino acid sequence of human insulin-like growth factor I (IGF-I), a polypeptide isolated from serum, has been determined. IGF-I is a single chain polypeptide of 70 amino acid residues cross-linked by three disulfide bridges. The calculated molecular weight is 7649. IGF-I displays obvious homology to proinsulin: positions 1 to 29 are homologous to insulin B chain and positions 42 to 62 to insulin A chain. A shortened "connecting" peptide with 12 residues (positions 30 to 41) compared to 30 to 35 in proinsulins shows no homology to proinsulin C peptide. An octapeptide sequence at the COOH-terminal end is also a feature not found in proinsulins. The number of differences in amino acid positions between IGF-I and insulins suggests that duplication of the gene of the common ancestor of proinsulin and IGF occurred before the time of appearance of the vertebrates. Of the 19 residues known to be invariant in all insulins so far sequenced, only glutamine A5 and asparagine A21 are replaced in IGF-I by glutamic acid and alanine, respectively. The fact that all half-cystine and glycine residues and most nonpolar core residues of the insulin monomer are conserved is compatible with a three-dimensional structure of IGF-I similar to that of insulin.

0 comments Cited 98 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism.

B Valentinis, Michelle Ananda-Rajah, Joshua Cohen (1997)

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is known to block IGF action and inhibit cell growth. IGFBP-3 is thought to act by sequestering free IGFs or, possibly, act via a novel IGF-independent mechanism. Supporting its role as a primary growth inhibitor, IGFBP-3 production has been shown to be increased by cell growth-inhibitory agents, such as transforming growth factor-beta (TGF-beta), and the tumor suppressor gene p53. In this paper, we demonstrate, for the first time, a novel function of IGFBP-3 as an apoptosis-inducing agent and show that this action is mediated through an IGF.IGF receptor-independent pathway. In the p53 negative prostate cancer cell line, PC-3, the addition of recombinant IGFBP-3 resulted in a dose-dependent induction of apoptosis. 125I-IGFBP-3 bound with high affinity to specific proteins in PC-3 cell lysates and plasma membrane preparations. These membrane-associated molecules may serve as receptors that mediate the direct effect of IGFBP-3 on apoptosis. In addition, in an IGF receptor-negative mouse fibroblast cell line, treatment with recombinant IGFBP-3 as well as transfection of the IGFBP-3 gene induced apoptosis, suggesting that neither IGFs nor IGF receptors are required for this action. Furthermore, treatment with TGF-beta1, a known apoptosis-inducing agent, resulted in the induction of IGFBP-3 expression 6-12 h before the onset of apoptosis. This effect of TGF-beta1 was prevented by co-treatment with IGFBP-3-neutralizing antibodies or IGFBP-3-specific antisense thiolated oligonucleotides. These findings suggest that IGFBP-3 induces apoptosis through a novel pathway independent of either p53 or the IGF.IGF receptor-mediated cell survival pathway and that IGFBP-3 mediates TGF-beta1 induced apoptosis in PC-3 cells.

0 comments Cited 76 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Eur J Med Res

Journal ID (iso-abbrev): Eur. J. Med. Res

Title: European Journal of Medical Research

Publisher: BioMed Central

ISSN (Print): 0949-2321

ISSN (Electronic): 2047-783X

Publication date Collection: 2011

Publication date (Electronic): 10 October 2011

Volume: 16

Issue: 10

Pages: 451-456

Affiliations

[1 ]Department of Radiation Therapy and Radiooncology, universitätsklinikum Düsseldorf, Heinrich Heine universität, Duesseldorf, Germany

[2 ]Department of Dermatology, universitätsklinikum Düsseldorf, Heinrich Heine universität, Düsseldorf, Germany

[3 ]Department of General-, Visceral-, and Pediatric Surgery, universitätsklinikum Düsseldorf, Heinrich Heine Universität, Düsseldorf, Germany

[4 ]Institute of Molecular Medicine, Düsseldorf, Germany

[5 ]Department of Glinical Chemistry, university of Ulm, Germany

[6 ]Methodist Hospital, Houston, Texas, USA

[7 ]Department of Surgery, Hospital Biberach, Germany

[8 ]Department of Statistics, university of Dortmund, Germany

[9 ]Department of Gastroenterology, Universitatsklinikum Düsseldorf, Heinrich Heine Universitat, Düsseldorf, Germany

[10 ]Institute of Diagnostic and Interventional Radiology, University Hospital, Düsseldorf, Germany

[11 ]Childrenshospital, University of Tübingen, Tübingen, Germany

Article

Publisher ID: 2047-783X-16-10-451

DOI: 10.1186/2047-783X-16-10-451

PMC ID: 3400976

PubMed ID: 22024424

SO-VID: 9f1a8a5c-996d-4e2f-a446-bd0c88399f70

History

Date received : 14 June 2011

Date accepted : 6 July 2011

Comments

Comment on this article

scite_

Cited by 8

See all cited by

Most referenced authors 238

See all reference authors

Do insulin-like growth factor associated proteins qualify as a tumor marker? Results of a prospective study in 163 cancer patients

Read this article at

Abstract

Objective

Methods

Results

Conclusion

Related collections

Journal of Medical Education Research

Most cited references 37

Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations.

The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin.

Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 168

Cited by 8

Most referenced authors 238