Open Access Research

Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines

Cristian M Ortiz1*, Tetsuo Ito2, Yosuke Hashimoto3, Satoshi Nagayama4, Akira Iwai4, Shigeru Tsunoda4, Fumiaki Sato5, Miguel Martorell1, Jose Angel Garcia1, Ana Perez1 and Yutaka Shimada6

Author affiliations

1 Department of Pathology, Valencia University, Hospital General Universitario de Valencia, Avenida tres cruces N° 2, CP 46014, Valencia, Spain

2 Department of of Surgery, Sugita Genpaku Memorial Obama Municipal Hospital. 2-2 Ohte-cho, Obama, Fukui, 917-8567, Japan

3 Division of Colon and Rectal Surgery, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan

4 Department of Surgery, Graduate School of Medicine, Kyoto University, Kawaracho 54 Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

5 Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kawaracho 54 Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

6 Department of Surgery & Science. Graduate School of Medicine & Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

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Citation and License

Diagnostic Pathology 2010, 5:41  doi:10.1186/1746-1596-5-41

Published: 21 June 2010

Abstract

Background

Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation.

Methods

We examined whether fascin is a potential target in ESCC using in vitro and in vivo studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line.

Results

The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. In vivo, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation.

Conclusions

These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.