Tissue transgluaminase 2 expression in meningiomas.

Area of Science:

• Neuro-oncology
• Tumor microenvironment research
• Biochemistry of extracellular matrix

Background:

• Meningiomas are common intracranial tumors, often benign but clinically challenging.
• Standard treatments like surgery and radiation have limitations, as meningioma cells can resist apoptosis.
• Tumor cells modify extracellular matrix (ECM) proteins, such as fibronectin, influencing tumor progression.

Purpose of the Study:

• To investigate the expression and association of fibronectin and tissue transglutaminase 2 (TG2) in meningiomas.
• To evaluate the therapeutic potential of inhibiting TG2 in meningioma treatment.

Main Methods:

• Examined fibronectin and TG2 expression in meningioma samples.
• Assessed TG2 activity and its co-localization with fibronectin.
• Treated cultured meningioma cells and tumor explants with a TG2 inhibitor (KCC009).

Main Results:

• Both fibronectin and TG2 were highly expressed in all studied meningiomas.
• TG2 activity was elevated and co-localized with fibronectin.
• KCC009 treatment inhibited TG2-fibronectin binding, blocked fibronectin disposition, promoted apoptosis, and enhanced radiation sensitivity.

Conclusions:

• TG2 is strongly expressed and active in meningiomas, associating with fibronectin.
• Inhibiting TG2 with KCC009 demonstrates therapeutic potential by increasing apoptosis and radiosensitivity.
• TG2 may play a protective role in meningiomas, suggesting it as a therapeutic target.