Abstract
Controlled degradation of the extracellular matrix by proteases is crucial in tumor cell invasion. We have shown that thrombospondin-1 (TSP-1), through activation of transforming growth factor beta-1 (TGF-β1), regulates the plasminogen/plasmin protease system in breast cancer. To determine whether this occurred in other epithelial neoplasms, we studied the role of TSP-1 and TGF-β1 in the regulation of the plasminogen/plasmin system in pancreatic cancer. ASPC-1 and COLO-357 pancreatic cancer cells were treated with TSP-1 or TGF-β1 at varying concentrations. The TSP-1 and TGF-β1-treated cells were also treated with either anti-TSP-1, anti-TSP-1 receptor, or anti-TGF-β1 antibodies. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression was determined by enzyme-linked immunosorbent assay. TSP-1 and TGF-β1 promoted a dose-dependent upregulation of ASPC-1 and COLO-357 PAI-1 expression. The TSP-1 effect could be blocked with anti-TSP-1 or anti-TGF-β1 antibodies. The TGF-β1 effect could be blocked only with anti-TGF-β1 antibody. Anti-TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-β1-mediated PAI-1 expression. Neither TSP-1 nor TGF-β1 had an effect on uPA production. We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-β1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 411-417 |
| Number of pages | 7 |
| Journal | Journal of Gastrointestinal Surgery |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 1 1999 |
| Externally published | Yes |
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Keywords
- Pancreatic neoplasms
- Plasminogen activator inhibitor
- Thrombospondin-1
- Transforming growth factor beta-1
- Urokinase plasminogen activator
ASJC Scopus subject areas
- Surgery
- Gastroenterology
Cite this
Thrombospondin-1 and Transforming Growth Factor Beta-1 Upregulate Plasminogen Activator Inhibitor Type 1 in Pancreatic Cancer. / Albo, Daniel; Berger, David H.; Vogel, Jon; Tuszynski, George P.
In: Journal of Gastrointestinal Surgery, Vol. 3, No. 4, 01.01.1999, p. 411-417.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thrombospondin-1 and Transforming Growth Factor Beta-1 Upregulate Plasminogen Activator Inhibitor Type 1 in Pancreatic Cancer
AU - Albo, Daniel
AU - Berger, David H.
AU - Vogel, Jon
AU - Tuszynski, George P.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - Controlled degradation of the extracellular matrix by proteases is crucial in tumor cell invasion. We have shown that thrombospondin-1 (TSP-1), through activation of transforming growth factor beta-1 (TGF-β1), regulates the plasminogen/plasmin protease system in breast cancer. To determine whether this occurred in other epithelial neoplasms, we studied the role of TSP-1 and TGF-β1 in the regulation of the plasminogen/plasmin system in pancreatic cancer. ASPC-1 and COLO-357 pancreatic cancer cells were treated with TSP-1 or TGF-β1 at varying concentrations. The TSP-1 and TGF-β1-treated cells were also treated with either anti-TSP-1, anti-TSP-1 receptor, or anti-TGF-β1 antibodies. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression was determined by enzyme-linked immunosorbent assay. TSP-1 and TGF-β1 promoted a dose-dependent upregulation of ASPC-1 and COLO-357 PAI-1 expression. The TSP-1 effect could be blocked with anti-TSP-1 or anti-TGF-β1 antibodies. The TGF-β1 effect could be blocked only with anti-TGF-β1 antibody. Anti-TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-β1-mediated PAI-1 expression. Neither TSP-1 nor TGF-β1 had an effect on uPA production. We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-β1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production.
AB - Controlled degradation of the extracellular matrix by proteases is crucial in tumor cell invasion. We have shown that thrombospondin-1 (TSP-1), through activation of transforming growth factor beta-1 (TGF-β1), regulates the plasminogen/plasmin protease system in breast cancer. To determine whether this occurred in other epithelial neoplasms, we studied the role of TSP-1 and TGF-β1 in the regulation of the plasminogen/plasmin system in pancreatic cancer. ASPC-1 and COLO-357 pancreatic cancer cells were treated with TSP-1 or TGF-β1 at varying concentrations. The TSP-1 and TGF-β1-treated cells were also treated with either anti-TSP-1, anti-TSP-1 receptor, or anti-TGF-β1 antibodies. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression was determined by enzyme-linked immunosorbent assay. TSP-1 and TGF-β1 promoted a dose-dependent upregulation of ASPC-1 and COLO-357 PAI-1 expression. The TSP-1 effect could be blocked with anti-TSP-1 or anti-TGF-β1 antibodies. The TGF-β1 effect could be blocked only with anti-TGF-β1 antibody. Anti-TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-β1-mediated PAI-1 expression. Neither TSP-1 nor TGF-β1 had an effect on uPA production. We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-β1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production.
KW - Pancreatic neoplasms
KW - Plasminogen activator inhibitor
KW - Thrombospondin-1
KW - Transforming growth factor beta-1
KW - Urokinase plasminogen activator
UR - http://www.scopus.com/inward/record.url?scp=0033155804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033155804&partnerID=8YFLogxK
U2 - 10.1016/S1091-255X(99)80058-4
DO - 10.1016/S1091-255X(99)80058-4
M3 - Article
C2 - 10482694
AN - SCOPUS:0033155804
VL - 3
SP - 411
EP - 417
JO - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
JF - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
SN - 1091-255X
IS - 4
ER -