Thrombomodulin expression regulates tumorigenesis in bladder cancer

Area of Science:

• Oncology
• Molecular Biology

Background:

• Thrombomodulin (TM) is an endogenous anti-metastatic factor with diagnostic and prognostic value in carcinoma.
• TM is a sensitive urothelial marker, crucial for therapeutic planning and patient management in cancer.

Purpose of the Study:

• To investigate the role of Thrombomodulin (TM) in bladder cancer progression and its potential as a therapeutic target.
• To evaluate TM's predictive capacity for tumor invasiveness in bladder cancer patients.

Main Methods:

• In vitro studies using human bladder cancer cell lines (HT1376, HT1197, J82, T24) and in vivo animal models.
• Immunohistochemical staining of clinical specimens from 100 bladder cancer patients to assess TM expression and invasiveness.

Main Results:

• Positive TM immunoreactivity inversely correlated with clinical stage and DNA methyltransferase 1 levels.
• Decreased TM expression predicted aggressive tumor growth and advanced stage; TM inhibition augmented tumor growth, invasion, proliferation, epithelial-mesenchymal transition (EMT), and angiogenesis.
• NF-κB inhibition increased TM expression and reduced tumor aggressiveness.

Conclusions:

• Thrombomodulin (TM) significantly influences bladder cancer aggressiveness both in vitro and in vivo.
• TM is a clinically relevant predictor of bladder cancer invasiveness and a potential therapeutic target.