AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Transl Res 2009;1(2):115-130

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

David J. DeGraff, Adam A. Aguiar, Robert A. Sikes

Laboratory for Cancer Ontogeny and Therapeutics, Center for Translational Cancer Research, Department of
Biological Sciences, University of Delaware, Newark, DE 19716, USA

Received January 9, 2009; accepted January, 2009; available online January, 2009

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.

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

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Address all correspondence to:
Robert A. Sikes, PhD
Laboratory for Cancer Ontogeny and Therapeutics
Center for Translational Cancer Research
Department of Biological Sciences
University of Delaware
Newark, DE 19716