Thrombomodulin expression regulates tumorigenesis in bladder cancer

Chun Te Wu, Ying Hsu Chang, Paul Y. Lin, Wen Cheng Chen, Miao Fen Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

25 Scopus citations

Abstract

Background: The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer.Methods: We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness.Results: The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer.Conclusions: TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer.

Original languageEnglish
Article number375
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - 28 05 2014
Externally publishedYes

Keywords

  • Bladder cancer
  • DNMT1
  • Epithelial-mesenchymal transition (EMT)
  • Thrombomodulin

Fingerprint

Dive into the research topics of 'Thrombomodulin expression regulates tumorigenesis in bladder cancer'. Together they form a unique fingerprint.

Cite this