Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
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Moitza Principe1,2,*, Patrizia Ceruti1,2,*, Neng-Yao Shih3,*, Michelle S. Chattaragada1,2, Simona Rolla1,2, Laura Conti2,4, Marco Bestagno5, Lorena Zentilin5, Sheng-Hui Yang6, Paola Migliorini7, Paola Cappello1,2, Oscar Burrone5 and Francesco Novelli1,2
1 Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy
2 Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
3 National Institute of Cancer Research, National Health Research Institutes, Tainan City, Taiwan
4 Molecular Biotechnology Center (MBC), University of Turin, Turin, Italy
5 International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
6 College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan
7 Department of Clinical and Experimental Medicine, University of Pisa, Italy
* These authors contributed equally to this work
Francesco Novelli, email:
Keywords: pancreatic cancer, ENO1, plasminogen, monoclonal antibody, adeno-associated virus
Received: February 05, 2015 Accepted: February 22, 2015 Published: March 14, 2015
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by rapid progression, invasiveness and resistance to treatment. We have previously demonstrated that most PDAC patients have circulating antibodies against the glycolytic enzyme alpha-enolase (ENO1), which correlates with a better response to therapy and survival. ENO1 is a metabolic enzyme, also expressed on the cell surface where it acts as a plasminogen receptor. ENO1 play a crucial role in cell invasion and metastasis by promoting plasminogen activation into plasmin, a serine-protease involved in extracellular matrix degradation. The aim of this study was to investigate the role of ENO1 in PDAC cell invasion. We observed that ENO1 was expressed on the cell surface of most PDAC cell lines. Mouse anti-human ENO1 monoclonal antibodies inhibited plasminogen-dependent invasion of human PDAC cells, and their metastatic spreading in immunosuppressed mice was inhibited. Notably, a single administration of Adeno-Associated Virus (AAV)-expressing cDNA coding for 72/1 anti-ENO1 mAb reduced the number of lung metastases in immunosuppressed mice injected with PDAC cells. Overall, these data indicate that ENO1 is involved in PDAC cell invasion, and that administration of an anti-ENO1 mAb can be exploited as a novel therapeutic option to increase the survival of metastatic PDAC patients.
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