Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-βs (TGF-βs). To determine whether TGF-βs can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-β receptor (sTβRII) that blocks cellular responsiveness to TGF-β1. When injected s.c. in athymic mice, PANC-1 clones expressing sTβRII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-βs act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sTβRII may ultimately have a therapeutic benefit in PDAC.
|Original language||English (US)|
|Number of pages||7|
|Journal||Molecular cancer therapeutics|
|State||Published - Jan 1 2002|
ASJC Scopus subject areas
- Cancer Research