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Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
07:59

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1

Published on: December 5, 2020

Genetic and pharmacologic inhibition of complement impairs endothelial cell function and ablates ovarian cancer

Selene Nunez-Cruz1, Phyllis A Gimotty, Matthew W Guerra

  • 1Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Neoplasia (New York, N.Y.)
|December 11, 2012
PubMed

Insights

Complement inhibition, by targeting complement factor 3 (C3) or C5a receptor (C5aR), significantly reduces ovarian tumor growth. This occurs by impairing endothelial cell function and altering vascular endothelial growth factor (VEGF) expression, highlighting complement

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Complement activation is crucial for regulating inflammatory responses.
  • The role of complement in ovarian cancer progression requires further elucidation.
  • Genetic complement deficiencies were investigated in a transgenic epithelial ovarian cancer model.

Purpose of the Study:

  • To assess the impact of complement factor 3 (C3) and C5a receptor (C5aR) deficiency on ovarian cancer development.
  • To investigate the effects of complement deficiency on tumor-infiltrating immune cells and cytokine production.
  • To determine the role of complement in endothelial cell (EC) function and angiogenesis within the tumor microenvironment.

Main Methods:

  • Generation of transgenic mice with epithelial ovarian cancer (TgMISIIR-TAg) crossed with mice deficient in C3 or C5aR.
  • Analysis of tumor incidence, size, vascularization, and immune cell infiltration.
  • Assessment of EC function, angiogenesis, and vascular endothelial growth factor (VEGF) isoform expression.

Main Results:

  • Mice deficient in C3 or C5aR exhibited significantly reduced tumor development or smaller, poorly vascularized tumors.
  • Immune cell composition varied, but cytokine production was reduced in C3-deficient tumors.
  • Endothelial cell function and angiogenesis were impaired in C3- and C5aR-deficient mice, linked to VEGF(165) expression.

Conclusions:

  • Complement inhibition, specifically targeting C3 or C5aR, effectively blocks ovarian tumor outgrowth.
  • The anti-tumor effect is mediated by impaired endothelial cell function and altered VEGF(165) expression.
  • Targeting the complement system presents a potential therapeutic strategy for ovarian cancer.

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