Related Experiment Video

Updated: Jul 20, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of

B Liu1, K-W Lee, M Anzo

  • 1Division of Pediatric Endocrinology, Department of Pediatrics, Mattel Children's Hospital, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.

Oncogene
|September 20, 2006
PubMed

Insights

Insulin-like growth factor-binding protein-3 (IGFBP-3) directly inhibits tumor growth and angiogenesis, independent of insulin-like growth factor (IGF) signaling. This protein suppresses tumor vascularization, supporting its potential as a prostate cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Insulin-like growth factor-binding protein-3 (IGFBP-3) is known to induce apoptosis through IGF-dependent and -independent pathways.
  • IGFBP-3's role in regulating tumor growth and angiogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the direct effects of IGFBP-3 on tumor growth and angiogenesis.
  • To determine whether the antiangiogenic effects of IGFBP-3 are dependent on IGF signaling.

Main Methods:

  • Human prostate cancer xenograft model in immunodeficient mice.
  • In vitro matrigel assays with human umbilical vein endothelial cells.
  • In vivo assays including matrigel plug and chick allantoic membrane models.
  • Zebrafish embryo model for angiogenesis studies.

Main Results:

  • IGFBP-3 injections reduced tumor size, increased apoptosis, and decreased tumor vascularity (CD31 staining).
  • IGFBP-3 inhibited endothelial cell network formation in vitro, independent of IGF.
  • In vivo models confirmed potent antiangiogenic actions of IGFBP-3.
  • Zebrafish studies demonstrated IGFBP-3's antiangiogenic effect is IGF-independent.

Conclusions:

  • IGFBP-3 exhibits direct, IGF-independent inhibitory effects on angiogenesis.
  • This antiangiogenic mechanism contributes to IGFBP-3's tumor-suppressive properties.
  • IGFBP-3 shows promise for clinical development in prostate cancer therapy.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...