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Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications
Exchange of molecules via exosomes is a means of eukaryotic intercellular communication, especially within tumour microenvironments. However, no data are available on alterations of exosomal molecular cargo by environmental cues (eg, pharmacological treatments). To approach this issue, we compared t...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278285/ https://www.ncbi.nlm.nih.gov/pubmed/25594007 |
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author | Ragusa, Marco Statello, Luisa Maugeri, Marco Barbagallo, Cristina Passanisi, Roberta Alhamdani, Mohamed S. Destri, Giovanni Li Cappellani, Alessandro Barbagallo, Davide Scalia, Marina Valadi, Hadi Hoheisel, Jörg D. Di Pietro, Cinzia Purrello, Michele |
author_facet | Ragusa, Marco Statello, Luisa Maugeri, Marco Barbagallo, Cristina Passanisi, Roberta Alhamdani, Mohamed S. Destri, Giovanni Li Cappellani, Alessandro Barbagallo, Davide Scalia, Marina Valadi, Hadi Hoheisel, Jörg D. Di Pietro, Cinzia Purrello, Michele |
author_sort | Ragusa, Marco |
collection | PubMed |
description | Exchange of molecules via exosomes is a means of eukaryotic intercellular communication, especially within tumour microenvironments. However, no data are available on alterations of exosomal molecular cargo by environmental cues (eg, pharmacological treatments). To approach this issue, we compared the abundance of 754 miRNAs and 741 cancer-related proteins in exosomes secreted by Caco-2 (Cetuximab-responsive) and HCT- 116 (Cetuximab-resistant) CRC cells, before and after Cetuximab treatment, with that in their source cells. Cetuximab significantly altered the cargo of Caco-2 exosomes: it increased abundance of miRNAs and proteins activating proliferation and inflammation and reduced miRNAs and proteins related to immune suppression. These alterations did not precisely mirror those in source cells, suggesting a Cetuximab-linked effect. Analogous alterations were detected in HCT-116. Transfection of exosomes from Cetuximab-treated Caco-2 into HCT-116 significantly increased HCT-116 viability; conversely, no viability alteration was detected in Caco-2 transfected with exosomes from Cetuximab-treated HCT-116. Analysis of networks, comprising targets of differentially expressed (DE) exosomal miRNAs and DE exosomal proteins, demonstrates a significant involvement of processes related to proliferation, inflammation, immune response, apoptosis. Our data extend existing knowledge on molecular mechanisms of eukaryotic intercellular communication, especially in oncological processes. Their translation to clinical settings may add new weapons to existing therapeutic repertoires against cancer. |
format | Online Article Text |
id | pubmed-4278285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42782852015-01-15 Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications Ragusa, Marco Statello, Luisa Maugeri, Marco Barbagallo, Cristina Passanisi, Roberta Alhamdani, Mohamed S. Destri, Giovanni Li Cappellani, Alessandro Barbagallo, Davide Scalia, Marina Valadi, Hadi Hoheisel, Jörg D. Di Pietro, Cinzia Purrello, Michele Oncoscience Research Paper Exchange of molecules via exosomes is a means of eukaryotic intercellular communication, especially within tumour microenvironments. However, no data are available on alterations of exosomal molecular cargo by environmental cues (eg, pharmacological treatments). To approach this issue, we compared the abundance of 754 miRNAs and 741 cancer-related proteins in exosomes secreted by Caco-2 (Cetuximab-responsive) and HCT- 116 (Cetuximab-resistant) CRC cells, before and after Cetuximab treatment, with that in their source cells. Cetuximab significantly altered the cargo of Caco-2 exosomes: it increased abundance of miRNAs and proteins activating proliferation and inflammation and reduced miRNAs and proteins related to immune suppression. These alterations did not precisely mirror those in source cells, suggesting a Cetuximab-linked effect. Analogous alterations were detected in HCT-116. Transfection of exosomes from Cetuximab-treated Caco-2 into HCT-116 significantly increased HCT-116 viability; conversely, no viability alteration was detected in Caco-2 transfected with exosomes from Cetuximab-treated HCT-116. Analysis of networks, comprising targets of differentially expressed (DE) exosomal miRNAs and DE exosomal proteins, demonstrates a significant involvement of processes related to proliferation, inflammation, immune response, apoptosis. Our data extend existing knowledge on molecular mechanisms of eukaryotic intercellular communication, especially in oncological processes. Their translation to clinical settings may add new weapons to existing therapeutic repertoires against cancer. Impact Journals LLC 2014-03-16 /pmc/articles/PMC4278285/ /pubmed/25594007 Text en Copyright: © 2014 Ragusa 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 Ragusa, Marco Statello, Luisa Maugeri, Marco Barbagallo, Cristina Passanisi, Roberta Alhamdani, Mohamed S. Destri, Giovanni Li Cappellani, Alessandro Barbagallo, Davide Scalia, Marina Valadi, Hadi Hoheisel, Jörg D. Di Pietro, Cinzia Purrello, Michele Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications |
title | Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications |
title_full | Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications |
title_fullStr | Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications |
title_full_unstemmed | Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications |
title_short | Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications |
title_sort | highly skewed distribution of mirnas and proteins between colorectal cancer cells and their exosomes following cetuximab treatment: biomolecular, genetic and translational implications |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278285/ https://www.ncbi.nlm.nih.gov/pubmed/25594007 |
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