Overexpression of MicroRNA-1 in Prostate Cancer Cells Modulates the Blood Vessel System of an In Vivo Hen's Egg Test-Chorioallantoic Membrane Model

In Vivo. 2019 Jan-Feb;33(1):41-46. doi: 10.21873/invivo.11436.

Abstract

Background/aim: In prostate cancer (PC), the formation of new blood vessels is stimulated by hypoxic conditions, androgens, and a number of molecular factors including microRNAs. MicroRNA-1 (miR-1) has been characterized in some tumor entities as anti-angiogenic, but this has not yet been investigated in PC.

Materials and methods: PC cells stably overexpressing miR-1 (LNCaP-miR-1) were incubated on an in vivo hen's egg test-chorioallantoic membrane (HET-CAM) model and compared to maternal LNCaP cells. Cell growth, blood vessel organisation, and total blood vessel area were analysed.

Results: Both matrigel-embedded LNCaP and LNCaP-miR-1 cells formed compact tumor-like cell aggregates on the CAM of the HET-CAM model. Although not quantifiable, bleeding of the CAM and remodelling of the blood vessel network in the CAM indicated an influence of miR-1 on the vascular system. The statistically significant decrease in the total surface area of blood vessels in the visible CAM section to 79.4% of control cells demonstrated the antiangiogenic properties of miR-1 for the first time.

Conclusion: MiR-1 had a tumor-suppressive and anti-angiogenic effect in an in vivo PC model. In the clinic, miR-1-mediated anti-angiogenesis would result in reduced tumor supply and increased hypoxic stress inside the tumor. Thus, miR-1 restoration by nucleic acid-based miR-1 mimetics would represent a promising option for future PC therapy.

Keywords: MicroRNA-1; angiogenesis; hen's egg test–chorioallantoic membrane model; prostate cancer.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Blood Vessels / metabolism*
  • Blood Vessels / pathology
  • Cell Line, Tumor
  • Chickens
  • Chorioallantoic Membrane / metabolism*
  • Collagen / chemistry
  • Drug Combinations
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laminin / chemistry
  • Male
  • MicroRNAs / genetics*
  • Prostate / drug effects
  • Prostate / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proteoglycans / chemistry
  • Tumor Hypoxia

Substances

  • Angiogenesis Inhibitors
  • Drug Combinations
  • Laminin
  • MIRN1 microRNA, human
  • MicroRNAs
  • Proteoglycans
  • matrigel
  • Collagen