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CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584351/ https://www.ncbi.nlm.nih.gov/pubmed/37851808 http://dx.doi.org/10.1126/sciadv.adi0244 |
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author | Samain, Remi Maiques, Oscar Monger, Joanne Lam, Hoyin Candido, Juliana George, Samantha Ferrari, Nicola KohIhammer, Leonie Lunetto, Sophia Varela, Adrian Orgaz, Jose L. Vilardell, Felip Olsina, Jorge Juan Matias-Guiu, Xavier Sarker, Debashis Biddle, Adrian Balkwill, Frances R. Eyles, Jim Wilkinson, Robert W. Kocher, Hemant M. Calvo, Fernando Wells, Claire M. Sanz-Moreno, Victoria |
author_facet | Samain, Remi Maiques, Oscar Monger, Joanne Lam, Hoyin Candido, Juliana George, Samantha Ferrari, Nicola KohIhammer, Leonie Lunetto, Sophia Varela, Adrian Orgaz, Jose L. Vilardell, Felip Olsina, Jorge Juan Matias-Guiu, Xavier Sarker, Debashis Biddle, Adrian Balkwill, Frances R. Eyles, Jim Wilkinson, Robert W. Kocher, Hemant M. Calvo, Fernando Wells, Claire M. Sanz-Moreno, Victoria |
author_sort | Samain, Remi |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK–Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits. Mechanistically, CD73 activates RhoA–ROCK–Myosin II downstream of PI3K. Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73–ROCK–Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy. |
format | Online Article Text |
id | pubmed-10584351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105843512023-10-19 CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells Samain, Remi Maiques, Oscar Monger, Joanne Lam, Hoyin Candido, Juliana George, Samantha Ferrari, Nicola KohIhammer, Leonie Lunetto, Sophia Varela, Adrian Orgaz, Jose L. Vilardell, Felip Olsina, Jorge Juan Matias-Guiu, Xavier Sarker, Debashis Biddle, Adrian Balkwill, Frances R. Eyles, Jim Wilkinson, Robert W. Kocher, Hemant M. Calvo, Fernando Wells, Claire M. Sanz-Moreno, Victoria Sci Adv Biomedicine and Life Sciences Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK–Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits. Mechanistically, CD73 activates RhoA–ROCK–Myosin II downstream of PI3K. Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73–ROCK–Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy. American Association for the Advancement of Science 2023-10-18 /pmc/articles/PMC10584351/ /pubmed/37851808 http://dx.doi.org/10.1126/sciadv.adi0244 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Samain, Remi Maiques, Oscar Monger, Joanne Lam, Hoyin Candido, Juliana George, Samantha Ferrari, Nicola KohIhammer, Leonie Lunetto, Sophia Varela, Adrian Orgaz, Jose L. Vilardell, Felip Olsina, Jorge Juan Matias-Guiu, Xavier Sarker, Debashis Biddle, Adrian Balkwill, Frances R. Eyles, Jim Wilkinson, Robert W. Kocher, Hemant M. Calvo, Fernando Wells, Claire M. Sanz-Moreno, Victoria CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
title | CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
title_full | CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
title_fullStr | CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
title_full_unstemmed | CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
title_short | CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
title_sort | cd73 controls myosin ii–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584351/ https://www.ncbi.nlm.nih.gov/pubmed/37851808 http://dx.doi.org/10.1126/sciadv.adi0244 |
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