NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression.
Bottom Line: Furthermore, nardilysin expression was significantly associated with poorer prognosis (P = 0.0258).The invasiveness of NRD1-knockdown TE1 and TE5 esophageal cancer cell lines was less than that of the negative control siRNA-transfected cell lines.Expression of MMP2 and MMP3 mRNA was significantly lower in NRD1-knockdown TE5 cells than in negative control siRNA-transfected cells.
Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.Show MeSH
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Mentions: We performed immunohistochemical analysis, first in normal skeletal muscle in which abundant NRD1 mRNA expression was found, to serve as a positive control. Staining of nardilysin was observed in the normal skeletal muscle (Fig.2a), consistent with our qRT-PCR results. Next, we performed immunohistochemical analysis in 109 ESCC tissue samples. In non-neoplastic esophageal mucosa, only weak or negative staining of nardilysin was observed in squamous epithelial and stromal cells (Fig.2b). In contrast, ESCC tissue showed stronger or more extensive staining than corresponding non-neoplastic esophageal mucosa (Fig.2c). Staining of nardilysin was observed in the cytoplasm. Some ESCC cases showed heterogeneity of immunostaining of nardilysin, but a tendency for upregulation of nardilysin at the invasive front was not observed. Because some ESCC tissue samples showed heterogeneity of nardilysin immunostaining, we considered nardilysin staining to be positive when more than 10% of tumor cells were stained. In total, nardilysin-positive ESCC cases were found in 43 (39%) of 109 cases. We analyzed the relationship between nardilysin expression and clinicopathologic characteristics. Nardilysin-positive ESCC cases were more advanced in terms of T classification (P = 0.0007, χ2 test), N classification (P = 0.0164, χ2 test), and tumor stage (P < 0.0001, χ2 test) than nardilysin-negative ESCC cases (Table1). In addition, nardilysin-positive ESCC cases were more frequently found in moderately/poorly differentiated ESCC than in well differentiated ESCC cases (P = 0.0200, χ2 test). Expression of nardilysin was not associated with age or sex.
Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.