Inverse Expression of S100A4 and E-Cadherin Is Associated with Metastatic Potential in Gastric Cancer
2000
S100A4 is known to
be involved in cancer cell motility by virtue of its ability to
activate nonmuscle myosin. E-cadherin has an important role in the
homophilic cell-cell adhesion and is called an invasion suppressor
gene. In the current study, we investigate the histological type and
metastatic potential of gastric cancer from the aspect of the
interrelationship of E-cadherin and S100A4 expression. Expression of E-cadherin and S100A4 in gastric cancer cell lines,
primary gastric cancers, and their normal counterparts were analyzed by
reverse transcription-PCR, Western blot, and immunohistochemical
methods. S100A4 protein and E-cadherin were expressed in five of eight
gastric cancer cell lines, and inverse expression of the two proteins
are found in four cell lines. In the clinical specimens, E-cadherin
mRNA expression in differentiated adenocarcinomas (88%, 14 of 16) was
significantly more frequent than that in poorly differentiated
adenocarcinomas (50%, 22 of 44; P = 0.015).
Western blot analysis demonstrates that S100A4 protein expression in
poorly differentiated adenocarcinomas was 1.6-fold higher than in well
differentiated adenocarcinoma. Immunohistochemically, S100A4
expression was detected in 51 (55%) of 92 primary gastric cancers.
Reduced expression of E-cadherin in primary tumors was found in 66
(72%) of 92 tumors. S100A4 expression in the poorly differentiated
adenocarcinomas had a strong relation to positive lymph node
involvement or peritoneal dissemination. Reduced E-cadherin expression
showed a strong relationship with positive serosal involvement and
infiltrating type. Tumors classified as a group with reduced E-cadherin
and high expression of S100A4 reveal positive peritoneal dissemination,
serosal involvement, and infiltrating type in the growth pattern.
Furthermore, these tumors showed a strong correlation with the poorly
differentiated adenocarcinoma. In contrast, tumors with preserved
E-cadherin and low expression of S100A4 have a close relation to the
well differentiated adenocarcinoma and a favorable prognosis. By the
Cox proportional hazard model, S100A4 and E-cadherin tissue status was
judged as an independent prognostic factor. S100A4 and E-cadherin
tissue status may be a powerful aid in evaluating metastatic potential
or the prognosis of patients with gastric cancer.
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