Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by rapid progression, invasiveness and resistance to treatment. In our laboratory it has been demonstrated that most of PDAC patients have circulating antibodies against the glycolytic enzyme alpha-enolase. Alpha-enolase is not only a cytoplasmic enzyme but it is also expressed on cell surface where it acts as a plasminogen receptor. By promoting plasminogen activation into plasmin, a serine-protease involved in the extracellular matrix degradation, alpha- enolase could play a crucial role in cell invasion and metastatization. By cytofluorimetry we observed that alpha-enolase is expressed on most of PDAC cell lines. The aim of this study was to investigate its role in PDAC cell invasion. We found that treatment of the PDAC cell line CF-PAC-1 with a mouse monoclonal antibody against human alpha-enolase inhibited plasminogen-dependent migration through Matrigel, without influencing in vitro cell growth. To validate these results in vivo, SCID-beige mice were injected in the tail vein with luciferase expressing CF-PAC-1 cells and treated with anti-alpha- enolase monoclonal antibody or irrelevant mouse IgG as control. Mice treated with anti-alpha-enolase antibody displayed a reduced number of tumor mass compared to control IgG-treated mice. These data indicate that alpha-enolase is involved in the PDAC invasion suggesting that interference with enolase-plasminogen interaction could be useful to inhibit this process..

THE BLOCKADE OF PLASMINOGEN-ALPHA-ENOLASE INTERACTION INHIBITS THE INVASION OF PANCREATIC CANCER CELLS.

CERUTI, PATRIZIA;CAPPELLO, Paola;ROLLA, SIMONA;NOVELLI, Francesco
2010-01-01

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by rapid progression, invasiveness and resistance to treatment. In our laboratory it has been demonstrated that most of PDAC patients have circulating antibodies against the glycolytic enzyme alpha-enolase. Alpha-enolase is not only a cytoplasmic enzyme but it is also expressed on cell surface where it acts as a plasminogen receptor. By promoting plasminogen activation into plasmin, a serine-protease involved in the extracellular matrix degradation, alpha- enolase could play a crucial role in cell invasion and metastatization. By cytofluorimetry we observed that alpha-enolase is expressed on most of PDAC cell lines. The aim of this study was to investigate its role in PDAC cell invasion. We found that treatment of the PDAC cell line CF-PAC-1 with a mouse monoclonal antibody against human alpha-enolase inhibited plasminogen-dependent migration through Matrigel, without influencing in vitro cell growth. To validate these results in vivo, SCID-beige mice were injected in the tail vein with luciferase expressing CF-PAC-1 cells and treated with anti-alpha- enolase monoclonal antibody or irrelevant mouse IgG as control. Mice treated with anti-alpha-enolase antibody displayed a reduced number of tumor mass compared to control IgG-treated mice. These data indicate that alpha-enolase is involved in the PDAC invasion suggesting that interference with enolase-plasminogen interaction could be useful to inhibit this process..
2010
Targeting Cancer Invasion and Metastasis.
Miami, Florida, USA
February 21-24, 2010.
Targeting Cancer Invasion and Metastasis.
Pubblicazione a cura degli organizzatori del congresso
1
10
10
Patrizia Ceruti; Michelle Samuel Chattaragada; Paola Cappello; Moitza Principe; Jorg Hamm; Simona Rolla; Franco Novelli
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/87619
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