Angiostatin directly inhibits human prostate tumor cell invasion by blocking plasminogen binding to its cellular...

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Plasminogen 2epsilon enhances prostate tumor cell invasiveness by binding to CD26, triggering a calcium signaling cascade and upregulating matrix metalloproteinase-9.
• Angiostatin, a plasminogen fragment, inhibits endothelial cell proliferation, suggesting a potential role in cancer therapy.

Purpose of the Study:

• To investigate the inhibitory effect of angiostatin derived from plasminogen 2 glycoforms on 1-LN prostate tumor cell invasiveness.
• To determine if angiostatin 2epsilon directly inhibits tumor cell invasion and explore its mechanism of action.

Main Methods:

• Studied the binding of individual plasminogen 2 glycoform-derived angiostatins to CD26 on 1-LN cells.
• Assessed the impact of angiostatin 2epsilon on calcium signaling, matrix metalloproteinase-9 expression, and Matrigel invasion.
• Evaluated the effect of angiostatin 2epsilon on endothelial cell proliferation and tubule formation in vitro.

Main Results:

• Angiostatin 2epsilon was identified as the sole glycoform that binds to CD26 on 1-LN cells, competitively inhibiting plasminogen 2epsilon binding.
• This binding blocked the plasminogen 2epsilon-induced calcium signaling cascade, suppressed matrix metalloproteinase-9 expression, and inhibited 1-LN cell invasion of Matrigel.
• Angiostatin 2epsilon also inhibited in vitro endothelial cell proliferation and tubule formation.

Conclusions:

• Angiostatin 2epsilon directly inhibits prostate tumor cell invasiveness by interfering with the plasminogen 2epsilon-CD26 interaction.
• These findings indicate that angiostatin 2epsilon possesses a dual mechanism against cancer progression: inhibiting tumor vascularization and directly blocking tumor cell metastasis.