Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer

Int J Oncol. 2000 Jun;16(6):1125-31. doi: 10.3892/ijo.16.6.1125.


S100A4 has been implicated in the malignant phenotype of tumor cells, including cell motility, but the biological function is hardly known. A recent study suggests that S100A4-induced invasiveness in malignant tumor cells is partially caused by down-regulation of E-cadherin. To clarify the clinical significance of S100A4 and its association with E-cadherin-mediated cell-to-cell adhesion system, we examined their protein expressions in non-small cell lung cancer (NSCLC) specimens using immunohistochemical techniques. Expression of S100A4 was observed in 81 (60%) of 135 NSCLCs and correlated with progression of the pathological T factor (p<0.001), lymph node metastasis (p<0.005), and poor survival (p<0.05). Reduced expression of E-cadherin, alpha-catenin, and beta-catenin was observed in 64% (87 of 135), 50% (43 of 86), and 58% (50 of 86) of the specimens tested, respectively. The expression of E-cadherin closely correlated with differentiation and inversely with that of S100A4. Among these adhesion-associated molecules we found that alpha-catenin appeared to reflect most strikingly the presence of lymph node metastasis and the short survival periods of NSCLC patients. Furthermore, patients who showed S100A4-positive/alpha-catenin-negative expression had a significantly shorter survival than the patients with S100A4-negative/alpha-catenin-positive expression. These results indicate that S100A4, as well as alpha-catenin, plays a role in the progression and metastasis of NSCLCs and that simultaneous immunohistochemical detection of their expression may be useful to define a subpopulation of lung cancer patients with a possible poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cadherins / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cytoskeletal Proteins / metabolism
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / metabolism*
  • Trans-Activators*
  • alpha Catenin
  • beta Catenin


  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Neoplasm Proteins
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • S100A4 protein, human