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Degraff DJ, Aguiar AA, Sikes RA. Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. Am J Transl Res. 2009;1(2):115-30
Degraff, D. J., Aguiar, A. A., & Sikes, R. A. (2009). Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. American journal of translational research, 1(2), 115-30.
Degraff, David J, et al. "Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions." American journal of translational research vol. 1,2 (2009): 115-30.
Degraff DJ, Aguiar AA, Sikes RA. Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. Am J Transl Res. 2009 Jan 20;1(2):115-30. PMID: 19956425; PMCID: PMC2776314.
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Am J Transl Res. 2009 Jan 20;1(2):115-30.

Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions.

American journal of translational research

David J Degraff, Adam A Aguiar, Robert A Sikes

Affiliations

  1. Laboratory for Cancer Ontogeny and Therapeutics, Center for Translational Cancer Research, Department of Biological Sciences, University of Delaware 19716.

PMID: 19956425 PMCID: PMC2776314

Abstract

Accumulating evidence indicates that alterations in the IGF axis contribute to the development of chemo- and radio-resistant, advanced-stage cancers. Additionally, they contribute to hormonal insensitivity in adenocarcinomas such as those derived from prostate and breast. The ligands, IGF-I and IGF-II, along with their receptors, IGF-IR and IGF-IIR, have been implicated in a wide range of disease. Activation and subsequent signal transduction through the receptors is attenuated, and/or potentiated, by the interactions of IGF axis ligands, IGF-I/II, with the high affinity IGF-binding proteins 1 to 6 (IGFBP1-6). New evidence indicates that the IGFBPs, irrespective of ligand interactions, correlate with the development and metastatic behavior of several cancers. Increased expression of insulin-like growth factor binding protein 2 (IGFBP-2) is found in advanced cancers of the ovary, breast, stomach, adrenal gland, bladder, CNS, and prostate. Further, IGFBP-2 seemingly has ligand-independent effects that participate in the development and dissemination of advanced cancer cells. As such, IGFBP-2 can assist in the development of the lethal phenotype for some cancers. While several reports have shown an important role for IGFBP-2 in the development of androgen insensitivity and the proliferation of AI PCa cells in vivo, these studies have not tested a role for IGFBP-2 in the metastatic spread of AI PCa cells. Additionally, the mechanism of IGFBP-2 action in these events has not been elucidated. The redundancy and abundance of the IGFBPs have precluded a clear understanding of the means by which IGFBP-2 signals. Components of these signaling pathways, particularly IGFBP-2, are being evaluated currently in clinical trials.

Keywords: Insulin-like growth factor, IGF; androgen insensitivity, AI; androgen sensitive, AS; neoplasm, bone, metastasis; prostate cancer, PCa

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