Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer

Abstract Background Circulating tumor cells (CTCs) are pivotal in cancer progression, and in vitro CTC models are crucial for understanding their biological mechanisms. This study focused on the characterization of extracellular vesicles (EVs) from CTC lines derived from a patient with metastatic co...

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Main Authors: Luis Enrique Cortés-Hernández, Zahra Eslami-S, Aurore Attina, Silvia Batista, Laure Cayrefourcq, Jérôme Vialeret, Dolores Di Vizio, Christophe Hirtz, Bruno Costa-Silva, Catherine Alix-Panabières
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Experimental & Clinical Cancer Research
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Online Access:https://doi.org/10.1186/s13046-025-03360-4
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author Luis Enrique Cortés-Hernández
Zahra Eslami-S
Aurore Attina
Silvia Batista
Laure Cayrefourcq
Jérôme Vialeret
Dolores Di Vizio
Christophe Hirtz
Bruno Costa-Silva
Catherine Alix-Panabières
author_facet Luis Enrique Cortés-Hernández
Zahra Eslami-S
Aurore Attina
Silvia Batista
Laure Cayrefourcq
Jérôme Vialeret
Dolores Di Vizio
Christophe Hirtz
Bruno Costa-Silva
Catherine Alix-Panabières
author_sort Luis Enrique Cortés-Hernández
collection DOAJ
description Abstract Background Circulating tumor cells (CTCs) are pivotal in cancer progression, and in vitro CTC models are crucial for understanding their biological mechanisms. This study focused on the characterization of extracellular vesicles (EVs) from CTC lines derived from a patient with metastatic colorectal cancer (mCRC) at different stages of progression who progressed despite therapy (thus mirroring the clonal evolution of cancer). Methods and results Morphological and size analyses revealed variations among EVs derived from different CTC lines. Compared with the Vesiclepedia database, proteomic profiling of these EVs revealed enrichment of proteins related to stemness, endosomal biogenesis, and mCRC prognosis. Integrin family proteins were significantly enriched in EVs from CTC lines derived after therapy failure. The role of these EVs in cancer progression was analyzed by assessing their in vivo distribution, particularly in the liver, lungs, kidneys, and bones. EVs accumulate significantly in the liver, followed by the lungs, kidneys and femurs. Conclusions This study is a pioneering effort in highlighting therapy progression-associated changes in EVs from mCRC patients via an in vitro CTC model. The results offer insights into the role of metastasis initiator CTC-derived EVs in cancer spread, suggesting their utility for studying cancer tissue distribution mechanisms. However, these findings must be confirmed and extended to patients with mCRC. This work underscores the potential of CTC-derived EVs as tools for understanding cancer dissemination.
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spelling doaj-art-54a9dd5b64574ff5b467ece1b2673d4f2025-08-20T03:06:58ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-03-0144111410.1186/s13046-025-03360-4Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancerLuis Enrique Cortés-Hernández0Zahra Eslami-S1Aurore Attina2Silvia Batista3Laure Cayrefourcq4Jérôme Vialeret5Dolores Di Vizio6Christophe Hirtz7Bruno Costa-Silva8Catherine Alix-Panabières9Laboratory of Rare Human Circulating Cells, University Medical Center of MontpellierLaboratory of Rare Human Circulating Cells, University Medical Center of MontpellierIRMB-PPC, INM, Univ Montpellier, CHU Montpellier, INSERM CNRSSystems Oncology Group, Champalimaud Centre for the UnknownLaboratory of Rare Human Circulating Cells, University Medical Center of MontpellierIRMB-PPC, INM, Univ Montpellier, CHU Montpellier, INSERM CNRSDepartment of Urology, Division of Cancer Biology and Therapeutics, Cedars-Sinai Medical CenterIRMB-PPC, INM, Univ Montpellier, CHU Montpellier, INSERM CNRSSystems Oncology Group, Champalimaud Centre for the UnknownLaboratory of Rare Human Circulating Cells, University Medical Center of MontpellierAbstract Background Circulating tumor cells (CTCs) are pivotal in cancer progression, and in vitro CTC models are crucial for understanding their biological mechanisms. This study focused on the characterization of extracellular vesicles (EVs) from CTC lines derived from a patient with metastatic colorectal cancer (mCRC) at different stages of progression who progressed despite therapy (thus mirroring the clonal evolution of cancer). Methods and results Morphological and size analyses revealed variations among EVs derived from different CTC lines. Compared with the Vesiclepedia database, proteomic profiling of these EVs revealed enrichment of proteins related to stemness, endosomal biogenesis, and mCRC prognosis. Integrin family proteins were significantly enriched in EVs from CTC lines derived after therapy failure. The role of these EVs in cancer progression was analyzed by assessing their in vivo distribution, particularly in the liver, lungs, kidneys, and bones. EVs accumulate significantly in the liver, followed by the lungs, kidneys and femurs. Conclusions This study is a pioneering effort in highlighting therapy progression-associated changes in EVs from mCRC patients via an in vitro CTC model. The results offer insights into the role of metastasis initiator CTC-derived EVs in cancer spread, suggesting their utility for studying cancer tissue distribution mechanisms. However, these findings must be confirmed and extended to patients with mCRC. This work underscores the potential of CTC-derived EVs as tools for understanding cancer dissemination.https://doi.org/10.1186/s13046-025-03360-4Extracellular vesiclesCirculating tumor cellsColorectal cancerProteomeCancer progressionLiquid biopsy
spellingShingle Luis Enrique Cortés-Hernández
Zahra Eslami-S
Aurore Attina
Silvia Batista
Laure Cayrefourcq
Jérôme Vialeret
Dolores Di Vizio
Christophe Hirtz
Bruno Costa-Silva
Catherine Alix-Panabières
Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer
Journal of Experimental & Clinical Cancer Research
Extracellular vesicles
Circulating tumor cells
Colorectal cancer
Proteome
Cancer progression
Liquid biopsy
title Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer
title_full Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer
title_fullStr Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer
title_full_unstemmed Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer
title_short Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer
title_sort proteomic profiling and functional analysis of extracellular vesicles from metastasis competent circulating tumor cells in colon cancer
topic Extracellular vesicles
Circulating tumor cells
Colorectal cancer
Proteome
Cancer progression
Liquid biopsy
url https://doi.org/10.1186/s13046-025-03360-4
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