Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer.
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.
Kimura
K
K
Department of Experimental Therapeutics, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan.
Endo
Y
Y
Yonemura
Y
Y
Heizmann
C W
CW
Schafer
B W
BW
Watanabe
Y
Y
Sasaki
T
T
D000368:Aged; D015820:Cadherins / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000556:secondary; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; C077591:S100A4 protein, human