Inhibition of Prostate Cancer Cell Migration and Invasion through Epidermal Growth Factor Receptor Pathway

Recent research published in the journal Oncogene has shed light on a potential therapeutic approach for prostate cancer. The study found that cleaved high-molecular-weight kininogen and its domain 5 can inhibit the migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway. The researchers discovered that the co-localization of urokinase-type plasminogen activator receptor and epidermal growth factor receptor on the surface of prostate cancer cells is prevented by high-molecular-weight kininogen. This inhibition results in a significant decrease in the phosphorylation of epidermal growth factor receptor and its downstream effectors, extracellular signal-regulated kinase and AKT. The study suggests that high-molecular-weight kininogen and its domain 5 may have therapeutic potential in reducing metastasis of human prostate cancer.

Key Takeaways:

• High-molecular-weight kininogen can be hydrolysed by plasma kallikrein to bradykinin and cleaved high-molecular-weight kininogen, which has potent anti-angiogenic activity.
• Cleaved high-molecular-weight kininogen and its domain 5 inhibit human prostate cancer cell migration by 76.0% and invasion by 78.0% at specific concentrations.
• The co-localization of urokinase-type plasminogen activator receptor and epidermal growth factor receptor on the surface of prostate cancer cells is prevented by high-molecular-weight kininogen.
• Immunoblotting shows that high-molecular-weight kininogen significantly decreases the bFGF-transactivated phosphorylation of epidermal growth factor receptor at Tyr 1173 between 30 min and 4 h.
• The phosphorylation of extracellular signal-regulated kinase and AKT, which are downstream effectors of epidermal growth factor receptor, is also inhibited by high-molecular-weight kininogen.
• The researchers concluded that high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through an EGFR/uPAR pathway.
• High-molecular-weight kininogen and its domain 5 may have therapeutic potential in reducing metastasis of human prostate cancer.

Statistics:

• 76.0% inhibition of human prostate cancer cell migration by cleaved high-molecular-weight kininogen at 300 nM.
• 78.0% inhibition of human prostate cancer cell invasion by cleaved high-molecular-weight kininogen at 11.1 nM.
• 30-120 minute phosphorylation of epidermal growth factor receptor by bFGF-transactivation.
• 4-hour phosphorylation of extracellular signal-regulated kinase and AKT by epidermal growth factor receptor.

Sources:

• Liu, Y., et al. (2009). Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway. Oncogene, 28(30), 2756-2765.
• Temple University, Research Center
• Prostate Cancer Genetics
• NewsRx.com
• Angiogenesis Weekly