Cargando…

Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells

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 correl...

Descripción completa

Detalles Bibliográficos
Autores principales: Principe, Moitza, Ceruti, Patrizia, Shih, Neng-Yao, Chattaragada, Michelle S., Rolla, Simona, Conti, Laura, Bestagno, Marco, Zentilin, Lorena, Yang, Sheng-Hui, Migliorini, Paola, Cappello, Paola, Burrone, Oscar, Novelli, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484442/
https://www.ncbi.nlm.nih.gov/pubmed/25860938
_version_ 1782378665009479680
author Principe, Moitza
Ceruti, Patrizia
Shih, Neng-Yao
Chattaragada, Michelle S.
Rolla, Simona
Conti, Laura
Bestagno, Marco
Zentilin, Lorena
Yang, Sheng-Hui
Migliorini, Paola
Cappello, Paola
Burrone, Oscar
Novelli, Francesco
author_facet Principe, Moitza
Ceruti, Patrizia
Shih, Neng-Yao
Chattaragada, Michelle S.
Rolla, Simona
Conti, Laura
Bestagno, Marco
Zentilin, Lorena
Yang, Sheng-Hui
Migliorini, Paola
Cappello, Paola
Burrone, Oscar
Novelli, Francesco
author_sort Principe, Moitza
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4484442
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-44844422015-07-10 Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells Principe, Moitza Ceruti, Patrizia Shih, Neng-Yao Chattaragada, Michelle S. Rolla, Simona Conti, Laura Bestagno, Marco Zentilin, Lorena Yang, Sheng-Hui Migliorini, Paola Cappello, Paola Burrone, Oscar Novelli, Francesco Oncotarget Research Paper 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. Impact Journals LLC 2015-03-14 /pmc/articles/PMC4484442/ /pubmed/25860938 Text en Copyright: © 2015 Principe et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Principe, Moitza
Ceruti, Patrizia
Shih, Neng-Yao
Chattaragada, Michelle S.
Rolla, Simona
Conti, Laura
Bestagno, Marco
Zentilin, Lorena
Yang, Sheng-Hui
Migliorini, Paola
Cappello, Paola
Burrone, Oscar
Novelli, Francesco
Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
title Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
title_full Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
title_fullStr Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
title_full_unstemmed Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
title_short Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
title_sort targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484442/
https://www.ncbi.nlm.nih.gov/pubmed/25860938
work_keys_str_mv AT principemoitza targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT cerutipatrizia targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT shihnengyao targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT chattaragadamichelles targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT rollasimona targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT contilaura targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT bestagnomarco targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT zentilinlorena targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT yangshenghui targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT migliorinipaola targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT cappellopaola targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT burroneoscar targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells
AT novellifrancesco targetingofsurfacealphaenolaseinhibitstheinvasivenessofpancreaticcancercells