Abstract
Fascin, an actin bundling protein, induces membrane protrusions and increased cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and the role of fascin in esophageal squamous cell carcinoma (ESCC) is still unknown. Paraffin sections of 200 patients with ESCC were immunohistochemically investigated. The expression levels of fascin mRNA in 20 ESCC tissues were compared with that in corresponding normal esophageal epithelium by semiquantitative reverse transcription-PCR. We also examined fascin protein expression in 33 ESCC cell lines. The role of fascin in cell motility and invasiveness in ESCC cells was assessed by the vector-based small interfering RNA. In immunohistochemical study, the intensity of fascin expression was usually increased in the tumor compared with that in normal epithelium. Fascin overexpression was significantly associated with a poor prognosis (immunoreactive rate, P = 0.033; immunoreactive intensity, P = 0.031). The fascin immunoreactive rate was associated with extent of the tumor (P = 0.002) and lymph node metastasis (P = 0.003). Multivariate analysis showed that fascin expression intensity was an independent prognostic factor, but the immunoreactive rate was not. In addition, up-regulation of fascin mRNA was found in 60% (12 of 20) of patients. In vitro study revealed that all 33 ESCC cell lines expressed fascin protein at a certain level. KYSE170, one of the fascin-overexpressed cells, decreased its motile and invasive properties after down-regulation of fascin expression. Our findings suggest that fascin overexpression may play an important role in the progression of ESCC.
Highlights
Fascin, an actin bundling protein, induces membrane protrusions and increased cell motility in various transformed cells
We first examined the distribution of fascin in the normal esophageal epithelium by antibody staining
Of the 200 patients with esophageal squamous cell carcinoma (ESCC), 145 (71.1%) patients were classified as 4+, >75% of positive staining, whereas 55 (28.9%) patients were classified as positive 1+, 2+, and 3+,
Summary
An actin bundling protein, induces membrane protrusions and increased cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and the role of fascin in esophageal squamous cell carcinoma (ESCC) is still unknown. Results: In immunohistochemical study, the intensity of fascin expression was usually increased in the tumor compared with that in normal epithelium. The fascin immunoreactive rate was associated with extent of the tumor (P = 0.002) and lymph node metastasis (P = 0.003). Invasive tumor cells often show specific morphologic features, such as the appearance of membrane protrusions as well as loss of cell-cell adhesion and loss of junctional communications, and These are thought to result from rearrangements of the cytoskeletal microfilaments by the action of actin cross-linking proteins (6 – 8). To determine whether fascin plays a role in ESCC, we examined a large number of surgical specimens of www.aacrjournals.org
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