Inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1

Olga Volpert1, Weiping Luo, Ta-Jen Liu

  • 1Department of Microbiology-Immunology, R. H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.

Insights

Carcinoma cell adhesion molecule CEACAM1 suppresses tumor growth by inhibiting angiogenesis. CEACAM1 expression in prostate cancer cells promotes the secretion of factors that block blood vessel formation and induce cancer cell death.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • Carcinoma cell adhesion molecule CEACAM1 previously identified as a tumor suppressor in prostate cancer.
  • CEACAM1 expression inhibits prostate cancer cell growth in vivo but not in vitro, suggesting a role in anti-angiogenesis.

Purpose of the Study:

  • To investigate the mechanism by which CEACAM1 suppresses tumor growth, specifically its effect on angiogenesis.
  • To determine if CEACAM1 induces the production of anti-angiogenic factors.

Main Methods:

  • Expression of CEACAM1 in DU145 prostate cancer cells.
  • Analysis of conditioned medium from CEACAM1-expressing cells for effects on endothelial and epithelial cells in vitro.
  • Assessment of conditioned medium's effect on corneal neovascularization in vivo.
  • Evaluation of endothelial cell apoptosis induction by conditioned medium.

Main Results:

  • Conditioned medium from CEACAM1-expressing cells inhibited endothelial cell growth, migration, and induced apoptosis.
  • CEACAM1 expression blocked endothelial cell migration towards vascular endothelial growth factor.
  • CEACAM1 inhibited basic fibroblast growth factor-induced corneal neovascularization in vivo.
  • Only CEACAM1 mutants suppressing tumor growth in vivo induced endothelial cell apoptosis.

Conclusions:

  • CEACAM1-mediated tumor suppression in prostate carcinoma is partly due to the inhibition of tumor angiogenesis.
  • CEACAM1 promotes the secretion of factors that specifically target endothelial cells, inhibiting neovascularization and inducing apoptosis.

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...
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...
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...
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...