Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells

Danilo Millimaggi1, Marianna Mari, Sandra D'Ascenzo

  • 1Department of Experimental Medicine, L'Aquila University, L'Aquila, Italy.

Neoplasia (New York, N.Y.)
|April 27, 2007
PubMed

Insights

Ovarian cancer cells release microvesicles containing CD147, a molecule that promotes blood vessel growth (angiogenesis) in endothelial cells. This CD147-mediated mechanism in microvesicles contributes to ovarian cancer progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs) are crucial for tumor invasion, angiogenesis, growth, and metastasis.
  • CD147, a transmembrane molecule highly expressed in tumor cells, regulates MMP expression in stromal cells, potentially driving cancer progression.

Purpose of the Study:

  • To investigate the role of CD147 in microvesicles shed by ovarian cancer cells.
  • To determine if these CD147-positive microvesicles promote angiogenesis in endothelial cells.

Main Methods:

  • Analyzing CD147 expression in microvesicles from ovarian carcinoma cell lines (OVCAR3, SKOV3, A2780, CABA I).
  • Assessing the proangiogenic effects of these microvesicles on human umbilical vein endothelial cells (HUVECs).
  • Utilizing small interfering RNA (siRNA) to downregulate CD147 in OVCAR3 cells and transfecting CD147 cDNA into CABA I cells.

Main Results:

  • Microvesicles from ovarian cancer cells (OVCAR3, SKOV3, A2780) expressed varying levels of CD147 and promoted HUVEC angiogenesis in a CD147-dependent manner.
  • Microvesicles from CABA I cells with low CD147 expression showed no significant angiogenic effect.
  • siRNA-mediated CD147 knockdown in OVCAR3 cells reduced the angiogenic potential of their microvesicles.
  • CD147 transfection into CABA I cells rendered their microvesicles angiogenic and capable of promoting MMP gene expression in HUVECs.

Conclusions:

  • Microvesicles shed by ovarian cancer cells can induce proangiogenic activities in endothelial cells.
  • This proangiogenic effect is mediated by CD147 expressed on these microvesicles.
  • CD147-positive microvesicles represent a novel mechanism by which ovarian cancer promotes angiogenesis and potentially contributes to tumor progression.

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