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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))...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
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.
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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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