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

David Degraff, Adam A. Aguiar, Robert A. Sikes

Research output: Contribution to journalReview article

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)115-130
Number of pages16
JournalAmerican Journal of Translational Research
Volume1
Issue number2
StatePublished - 2009

Fingerprint

Insulin-Like Growth Factor Binding Protein 2
Prostatic Neoplasms
Ligands
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Prostate
Neoplasms
Insulin-Like Growth Factor Binding Protein 1
Signal transduction
Adrenal Glands
Radio
Ovarian Neoplasms
Androgens
Redundancy
Signal Transduction
Stomach
Urinary Bladder
Adenocarcinoma
Breast

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Cancer Research
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

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title = "Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions",
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.",
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Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. / Degraff, David; Aguiar, Adam A.; Sikes, Robert A.

In: American Journal of Translational Research, Vol. 1, No. 2, 2009, p. 115-130.

Research output: Contribution to journalReview article

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