Expression of snail in pancreatic cancer promotes metastasis and chemoresistance.
BACKGROUND
Pancreatic cancer is a dreadful malignancy. Because of its tendency to metastasis and its resistance to chemotherapy, the prognosis remains poor. Snail is a transcriptional factor that endows epithelial cells with migratory and anti-apoptotic abilities. Its expression has been demonstrated in many tumors. We hypothesized that Snail may be expressed in pancreatic cancer, and it may confer invasive and chemoresistant properties.


RESULTS
We immunohistochemically examined Snail expression in pancreatic cancer and found that it was expressed in 20 of 56 (36%) samples of pancreatic cancer. The Snail expression had a close correlation with lymph node invasion and distant metastasis. After transfecting Snail cDNA into pancreatic cancer cell line Panc-1, we found that Snail triggered overt epithelial to mesenchymal transitions in Panc-1 cells. The tumor invasive ability in vitro was evaluated using a transwell invasive chamber. Snail dramatically promoted the invasive ability of Panc-1 cells. Chemosensitivity of Panc-1 cells to 5-fluorouracil or gemcitabine after Snail transfection was assayed by MTT cell proliferation assay. Overexpression of Snail enhanced the chemoresistance to 5-fluorouracil of gemcitabine at different dosages. Moreover, Snail-transfected Panc-1 cells produced more spontaneous metastasis than parental untransfected cells after orthotopically injected into the pancreas of nude mice.


CONCLUSIONS
Snail is expressed in pancreatic cancer; it confers enhanced invasive ability and chemoresistance to pancreatic cancer cells. Snail may be a marker for predicting the malignancy of pancreatic cancer. Further therapy target to Snail may be of great benefit to pancreatic cancer patients.
Yin
Tao
T
Pancreatic Center, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China.
Wang
Chunyou
C
Liu
Tao
T
Zhao
Gang
G
Zha
Yunhong
Y
Yang
Ming
M
D000818:Animals; D015820:Cadherins / Q000032:analysis; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis*; D014746:Vimentin / Q000032:analysis
D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin