title: Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells.
abstract: 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.
authors: Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Moitza
authors: M
authors: Principe
authors: Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Patrizia
authors: P
authors: Ceruti
authors: National Institute of Cancer Research, National Health Research Institutes, Tainan City, Taiwan.
authors: Neng-Yao
authors: NY
authors: Shih
authors: Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Michelle S
authors: MS
authors: Chattaragada
authors: Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Simona
authors: S
authors: Rolla
authors: Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.|Molecular Biotechnology Center (MBC), University of Turin, Turin, Italy.
authors: Laura
authors: L
authors: Conti
authors: International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
authors: Marco
authors: M
authors: Bestagno
authors: International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
authors: Lorena
authors: L
authors: Zentilin
authors: College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan.
authors: Sheng-Hui
authors: SH
authors: Yang
authors: Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors: Paola
authors: P
authors: Migliorini
authors: Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Paola
authors: P
authors: Cappello
authors: International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
authors: Oscar
authors: O
authors: Burrone
authors: Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Francesco
authors: F
authors: Novelli
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
keywords: ENO1; adeno-associated virus; monoclonal antibody; pancreatic cancer; plasminogen