Human endothelial cells expressing polyoma middle T induce tumors

Area of Science:

• Oncology
• Virology
• Cell Biology

Background:

• Murine polyomavirus middle T oncogene (PymT) transforms murine endothelial cells (EC), causing vascular tumors.
• Human vascular tumors share similarities with PymT-induced murine tumors.
• Understanding PymT's effect on human EC is crucial for cancer research.

Purpose of the Study:

• To investigate the in vitro and in vivo behavior of human umbilical cord vein EC expressing PymT.
• To determine if PymT can transform human EC and induce tumor formation.
• To compare the transient versus immortalizing effects of PymT in human versus murine EC.

Main Methods:

• Infection of human primary umbilical cord vein EC with pLX-PymT retrovirus to create PymT-EC.
• Tumorigenesis assays in nu/nu mice.
• In vitro analysis of EC markers, proliferation, urokinase-type plasminogen activator, and plasminogen activator inhibitor-1.
• Assessment of PymT protein levels and pp60c-src activation.

Main Results:

• PymT-EC formed hemangiomas in nu/nu mice, containing both human and mouse EC.
• PymT-EC maintained endothelial markers and showed increased proliferation.
• PymT-EC exhibited altered urokinase-type plasminogen activator and plasminogen activator inhibitor-1 balance.
• Unlike murine EC, human PymT-EC effects were transient, leading to senescence after 12-15 passages.

Conclusions:

• PymT can induce vascular tumors in mice using human EC, but the transformation is transient.
• Human EC expressing PymT exhibit temporary proliferation and tumor-forming capacity.
• PymT-induced senescence in human EC involves a decrease in middle T protein and pp60c-src activation.