TY - JOUR
T1 - Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells
AU - Kikuta, Kazuhiro
AU - Masamune, Atsushi
AU - Watanabe, Takashi
AU - Ariga, Hiroyuki
AU - Itoh, Hiromichi
AU - Hamada, Shin
AU - Satoh, Kennichi
AU - Egawa, Shinichi
AU - Unno, Michiaki
AU - Shimosegawa, Tooru
N1 - Funding Information:
This work was supported in part by Grant-in-Aid from Japan Society for the Promotion of Science (to K.K. and A.M.), by the Pancreas Research Foundation of Japan (to A.M. and to T.W.), by the Kanae Foundation for Life and Socio-Medical Science (to A. M.), by the Uehara Memorial Foundation (to A.M.), and by the Research Committee of Intractable Pancreatic Diseases provided by the Ministry of Health, Labour, and Welfare of Japan.
PY - 2010/12/17
Y1 - 2010/12/17
N2 - The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti-TGF-β-neutralizing antibody, excluding a central role of TGF-β in this process. In conclusion, PSCs promoted EMT in pancreatic cancer cells suggesting a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells.
AB - The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti-TGF-β-neutralizing antibody, excluding a central role of TGF-β in this process. In conclusion, PSCs promoted EMT in pancreatic cancer cells suggesting a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells.
KW - Desmoplastic reaction
KW - Fibrosis
KW - Pancreatic cancer
KW - Pancreatitis
KW - Stroma
UR - http://www.scopus.com/inward/record.url?scp=78650175637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650175637&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2010.11.040
DO - 10.1016/j.bbrc.2010.11.040
M3 - Article
C2 - 21081113
AN - SCOPUS:78650175637
VL - 403
SP - 380
EP - 384
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3-4
ER -