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Activated endothelial cells induce apoptosis in lymphoma cells

V Umansky1, M Bucur, V Schirrmacher

  • 1GERMAN CANC RES CTR,DIV CELLULAR IMMUNOL,TUMOR IMMUNOL PROGRAM,D-6900 HEIDELBERG,GERMANY.

International Journal of Oncology
|May 3, 2011
PubMed

Insights

Activated endothelial cells produce nitric oxide (NO), which kills metastatic lymphoma cells in vitro. This NO-mediated cytotoxicity involves inducing apoptosis, revealing a novel role for endothelial cells in eliminating cancer metastasis.

Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Previous studies indicated nitric oxide (NO) production by liver endothelial cells is linked to the regression of liver metastases.
  • The role of endothelial cells in directly eliminating metastatic cancer cells requires further investigation.

Purpose of the Study:

  • To investigate the in vitro nitric oxide (NO)-mediated cytotoxicity of endothelial cells against metastatic lymphoma cells.
  • To elucidate the mechanism of NO-induced tumor cell death and the role of apoptosis.

Main Methods:

  • Co-culture of activated bovine endothelial cells (BEC) with ESbL-lacZ lymphoma cells.
  • Measurement of NO synthesis and inhibition using N-G-monomethyl-L-arginine (NMMA).
  • Assessment of tumor cell death via propidium iodide staining and Flow-Assisted Genetic Sorting (FAGS) analysis; induction of apoptosis.

Main Results:

  • Activated BEC significantly increased NO production upon stimulation with TNF-alpha, which was blocked by NMMA.
  • Activated BEC exhibited cytotoxicity against metastatic lymphoma cells, evidenced by cell death.
  • This cytotoxicity was reduced by NMMA pretreatment and mimicked by NO donor glycerol trinitrate (GTN), indicating NO's crucial role.
  • Activated BEC induced apoptosis in lymphoma cells, largely mediated by NO.

Conclusions:

  • Endothelial cells, when activated, can exert NO-mediated cytotoxicity against metastatic lymphoma cells.
  • Nitric oxide plays a significant role in inducing apoptosis in tumor cells, contributing to anti-metastatic effects.
  • Endothelial cells possess a novel function in eliminating metastatic cells through the induction of programmed cell death.

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