SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo.
SNAIL, a potent repressor of E-cadherin expression, plays a key role in inducing epithelial-to-mesenchymal transition (EMT) in epithelial cells. During EMT, epithelial cells lose cell polarity and adhesion, and undergo drastic morphological changes acquiring highly migratory abilities. Although there is increasing evidence that EMT is involved in the progression of some human cancers, its significance in the progression of pancreatic cancer remains elusive. In Panc-1, a well-known human pancreatic cancer cell line in which EMT is triggered by TGF-β1 treatment, SNAIL and vimentin are highly expressed, whereas E-cadherin expression is scant. In contrast, another human pancreatic cancer cell line, BxPC3, in which SNAIL expression is not detected, has high levels of E-cadherin expression and does not undergo EMT upon TGF-β1 treatment. After transfecting the SNAIL gene into BxPC3, however, the cells undergo EMT with remarkable alterations in cell morphology and molecular expression patterns without the addition of any growth factors. Furthermore, in an orthotopic transplantation model using SCID mice, SNAIL-transfected BxPC3 displayed highly metastatic and invasive activities. In the immunohistochemical analysis of the tumor derived from the SNAIL-expressing BxPC3, alterations suggestive of EMT were observed in the invasive tumor front. SNAIL enabled BxPC3 to undergo EMT, endowing it with a highly malignant potential in vivo. These results indicate that SNAIL-mediated EMT may be relevant in the progression of pancreatic cancer, and SNAIL could be a molecular target for a pancreatic cancer intervention.
Nishioka
Ryohei
R
Second Department of Surgery, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Itoh
Shunji
S
Gui
Ting
T
Gai
Zhibo
Z
Oikawa
Kosuke
K
Kawai
Manabu
M
Tani
Masaji
M
Yamaue
Hiroki
H
Muragaki
Yasuteru
Y
D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin