Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive

Jennifer A Tuxhorn1, Stephanie J McAlhany, Feng Yang

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Cancer Research
|November 5, 2002
PubMed

Insights

Transforming growth factor-beta1 (TGF-beta1) regulates reactive stroma, promoting prostate tumor growth and angiogenesis. Inhibiting TGF-beta1 significantly reduced tumor size and blood vessel formation in xenograft models.

Area of Science:

  • Oncology
  • Cancer Biology
  • Prostate Cancer Research

Background:

  • Reactive stroma is known to promote LNCaP human prostate tumor growth and angiogenesis.
  • The specific regulators of reactive stroma remain largely unknown.
  • Transforming growth factor-beta1 (TGF-beta1) is a potential regulator of reactive stroma.

Purpose of the Study:

  • To investigate the role of TGF-beta1 in regulating reactive stroma.
  • To determine if TGF-beta1 influences angiogenesis and tumor growth in prostate cancer.
  • To assess the therapeutic potential of targeting TGF-beta1 in prostate tumor models.

Main Methods:

  • Generation of three-way differential reactive stroma xenograft tumors.
  • Treatment of tumors with TGF-beta1 latency-associated peptide (LAP) or a TGF-beta1 neutralizing antibody.
  • Assessment of microvessel density and tumor wet-weight.

Main Results:

  • Tumors treated with TGF-beta inhibitors showed reduced blood vessel formation.
  • Microvessel density in LAP-treated tumors decreased 3.5-fold compared to controls.
  • Average wet-weight of LAP-treated tumors was reduced by 46% relative to control tumors.

Conclusions:

  • TGF-beta1 plays a critical role in regulating reactive stroma.
  • TGF-beta1 signaling is essential for promoting angiogenesis and growth of prostate tumors.
  • Inhibition of TGF-beta1 demonstrates potential for reducing prostate tumor progression.