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Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer
Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXO(Ascites))...
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/PMC10672184/ https://www.ncbi.nlm.nih.gov/pubmed/38000030 http://dx.doi.org/10.1126/sciadv.adk1098 |
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author | Hyung, Sujin Ko, Jihoon Heo, You Jeong Blum, Steven M. Kim, Seung Tae Park, Se Hoon Park, Joon Oh Kang, Won Ki Lim, Ho Yeong Klempner, Samuel J. Lee, Jeeyun |
author_facet | Hyung, Sujin Ko, Jihoon Heo, You Jeong Blum, Steven M. Kim, Seung Tae Park, Se Hoon Park, Joon Oh Kang, Won Ki Lim, Ho Yeong Klempner, Samuel J. Lee, Jeeyun |
author_sort | Hyung, Sujin |
collection | PubMed |
description | Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXO(Ascites)) in cancer progression and use modified exosomes as resources for cancer therapy. EXO(Ascites) from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXO(Ascites) concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET-amplified GC, EXO(Ascites) contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived MET-amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a MET non-amplified GC model. MET-amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC. |
format | Online Article Text |
id | pubmed-10672184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106721842023-11-24 Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer Hyung, Sujin Ko, Jihoon Heo, You Jeong Blum, Steven M. Kim, Seung Tae Park, Se Hoon Park, Joon Oh Kang, Won Ki Lim, Ho Yeong Klempner, Samuel J. Lee, Jeeyun Sci Adv Biomedicine and Life Sciences Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXO(Ascites)) in cancer progression and use modified exosomes as resources for cancer therapy. EXO(Ascites) from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXO(Ascites) concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET-amplified GC, EXO(Ascites) contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived MET-amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a MET non-amplified GC model. MET-amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC. American Association for the Advancement of Science 2023-11-24 /pmc/articles/PMC10672184/ /pubmed/38000030 http://dx.doi.org/10.1126/sciadv.adk1098 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 NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Hyung, Sujin Ko, Jihoon Heo, You Jeong Blum, Steven M. Kim, Seung Tae Park, Se Hoon Park, Joon Oh Kang, Won Ki Lim, Ho Yeong Klempner, Samuel J. Lee, Jeeyun Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer |
title | Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer |
title_full | Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer |
title_fullStr | Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer |
title_full_unstemmed | Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer |
title_short | Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer |
title_sort | patient-derived exosomes facilitate therapeutic targeting of oncogenic met in advanced gastric cancer |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672184/ https://www.ncbi.nlm.nih.gov/pubmed/38000030 http://dx.doi.org/10.1126/sciadv.adk1098 |
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