PUBLICATION
Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis
- Authors
- Liu, B., Lee, K.W., Anzo, M., Zhang, B., Zi, X., Tao, Y., Shiry, L., Pollak, M., Lin, S., and Cohen, P.
- ID
- ZDB-PUB-060921-26
- Date
- 2007
- Source
- Oncogene 26(12): 1811-1819 (Journal)
- Registered Authors
- Keywords
- insulin-like growth factor-binding protein-3, prostate cancer, angiogenesis, apoptosis
- MeSH Terms
-
- Animals
- Cell Division/physiology*
- Cell Line
- Insulin-Like Growth Factor Binding Protein 3/physiology*
- Male
- Mice
- Mice, SCID
- Neovascularization, Pathologic*
- Prostatic Neoplasms/blood supply
- Prostatic Neoplasms/pathology*
- PubMed
- 16983336 Full text @ Oncogene
Citation
Liu, B., Lee, K.W., Anzo, M., Zhang, B., Zi, X., Tao, Y., Shiry, L., Pollak, M., Lin, S., and Cohen, P. (2007) Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis. Oncogene. 26(12):1811-1819.
Abstract
Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer.
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