Thrombomodulin (TM) plays a role in coagulation, inflammation, and cell adhesion. Reduction of TM expression
plays an important role in the tumor metastatic process; however, insufficient information is available regarding the
expression of TM in nonsmall cell lung cancer (NSCLC). Sixty NSCLC patients who underwent surgery were reviewed
for TM expression and multiple variables were assessed by univariate and multivariate analyses. The expression level of
TM and its metastatic ability were examined in vitro using the human NSCLC A549 cell line. TM expression in NSCLC
was significantly correlated with survival; the 5-yr survival rates of patients with high and low TM expression were
23% and 18% (P<0.01), respectively. Distribution of TM was detected predominantly in the normal lung tissue
compared with lung cancer tissue. Western blot analysis showed, on average, decreased expression levels of TM
protein in the lung cancer tissues of patients with NSCLC. An in vitro study also showed that overexpression of TM can
inhibit the invasiveness and migration ability of the A549 cell line, whereas silencing of TM significantly enhanced
these processes. This inhibition of cellular migration by overexpression of TM was significantly prevented by the
selective inhibitors of PI3K and Akt, but not by MAPK inhibitors. This study demonstrates that a decrease in TM
expression may be an indicator in the prognosis of NSCLC patients and provides new insights into the molecular
mechanisms of TM in the metastasis of NSCLC
