Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

被引:0
作者
M Anders
M Vieth
C Röcken
M Ebert
M Pross
S Gretschel
P M Schlag
B Wiedenmann
W Kemmner
M Höcker
机构
[1] Charité Medical School,Department of Internal Medicine, Division of Gastroenterology and Hepatology
[2] Campus Virchow,Department of Internal Medicine II
[3] Institute of Pathology,Department of Surgery
[4] Klinikum Bayreuth,Department of Surgery and Surgical Oncology
[5] Institute of Pathology,undefined
[6] Charité Medical School,undefined
[7] Charitéplatz 1,undefined
[8] Technical University of Munich,undefined
[9] Ismaninger Str. 22,undefined
[10] DRK Kliniken Berlin Köpenick,undefined
[11] Robert Rössle Clinic Charité,undefined
[12] Max Delbrück Center of Molecular Medicine,undefined
[13] Center of Anatomy and Integrative Neuroanatomy,undefined
[14] Charité Medical School,undefined
来源
British Journal of Cancer | 2009年 / 100卷
关键词
coxsackie adenovirus receptor; gastric cancer; prognosis; migration; invasion;
D O I
暂无
中图分类号
学科分类号
摘要
Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor.
引用
收藏
页码:352 / 359
页数:7
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