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Updated: Aug 6, 2026

Isolation and Culture Expansion of Tumor-specific Endothelial Cells
10:15

Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Published on: October 14, 2015

Intracellular signaling in tumor and endothelial cells: The expected and, yet again, the unexpected

Oliver Stoeltzing1, Funda Meric-Bernstam, Lee M Ellis

  • 1Department of Surgery and Surgical Oncology, University of Regensburg Medical Center, Regensburg 93053, Germany.

Cancer Cell
|August 15, 2006
PubMed

Insights

Sustained Akt activation in endothelial cells causes abnormal tumor blood vessels. Rapamycin treatment reverses these effects but shows complex impacts on the tumor microenvironment.

Area of Science:

  • Oncology
  • Vascular Biology
  • Molecular Biology

Background:

  • Tumor vasculature exhibits complex structural and functional abnormalities.
  • Endothelial cell (EC) signaling pathways, including PI3K/Akt/mTOR, are crucial in regulating blood vessel formation and function.
  • Vascular Endothelial Growth Factor (VEGF) signaling plays a significant role in tumor angiogenesis.

Purpose of the Study:

  • To investigate the role of sustained endothelial Akt activation in tumor vessel abnormalities.
  • To determine the effects of PI3K/Akt/mTOR signaling inhibition on aberrant tumor vasculature.
  • To explore the impact of rapamycin on tumor microenvironment components.

Main Methods:

  • Expression of constitutively activated Akt1 (myrAkt1) in endothelial cells.
  • Inhibition of PI3K/Akt/mTOR signaling using rapamycin.
  • Analysis of blood vessel structure and function in tumor models.
  • Evaluation of rapamycin's effects on various cell types within the tumor microenvironment.

Main Results:

  • Sustained endothelial Akt activation by myrAkt1 recapitulates complex tumor vessel abnormalities.
  • Rapamycin treatment reverses pathological effects of excess VEGF signaling by inhibiting Akt or mTOR in ECs.
  • Unexpected and complex effects of mTOR inhibition by rapamycin were observed in vivo across different cell types.

Conclusions:

  • Targeting endothelial Akt activation offers a potential strategy to normalize tumor vasculature.
  • Rapamycin's dual action on ECs and other tumor microenvironment cells necessitates careful consideration for therapeutic application.
  • Further research is needed to elucidate the paradoxical effects of rapamycin in the tumor context.

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