Proteomic profiling of extracellular vesicles and particles reveals the cellular response to cisplatin in NSCLC.
biomarker
cancer
extracellular vesicles
non small cell lung cancer
proteomic
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
24
08
2021
received:
21
07
2021
accepted:
25
08
2021
pubmed:
15
9
2021
medline:
27
1
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Cisplatin-based chemotherapy is a therapeutic strategy against non-small cell lung cancer (NSCLC). However, cancers relapse after chemotherapy due to a dormant state of residual cancer cells. Extracellular vesicles and particles (EVPs) are active carriers of proteins and nucleic acid. Here, we aimed to study the molecular alterations and proteomic characteristics of EPV in dormant and reactivated cancer cells induced by cisplatin. We used a short-term single dose of cisplatin to induce the dormant and reactivated cell status. We examined the gene expressional profiling and proteomic profiling of EVPs from dormant and reactivated cancer cells by RNA-sequencing and LC-MS/MS. We found substantial changes in gene expression and protein level in EVP. The genes with higher expression in dormant cancer cells were lipid transporter- and lipid metabolic-related genes. A total of 111 EVP proteins were upregulated in dormant cancer cells compared to those in control cells. Fifty differential expressed proteins (DEPs) were identified in EVPs from reactivated cancer cells compared to those in dormant cancer cells. Among the DEPs, we found that apolipoproteins such as APOA1 and APOE were significantly increased in dormant cancer cell-derived EVPs. Integration of EVP proteomes with transcriptional profiles of cancer cells revealed that the proteomic profiling of EVP derived from cancer cells can reflect the cellular status of cancer cells, which showed an activated lipid metabolism in dormant state. Lipoproteins enriched in EVPs reflect the activated lipid metabolism in dormant cancer cells and may provide potential biomarkers or therapeutic targets for cisplatin-based therapy.
Sections du résumé
BACKGROUND
Cisplatin-based chemotherapy is a therapeutic strategy against non-small cell lung cancer (NSCLC). However, cancers relapse after chemotherapy due to a dormant state of residual cancer cells. Extracellular vesicles and particles (EVPs) are active carriers of proteins and nucleic acid. Here, we aimed to study the molecular alterations and proteomic characteristics of EPV in dormant and reactivated cancer cells induced by cisplatin.
METHODS
We used a short-term single dose of cisplatin to induce the dormant and reactivated cell status. We examined the gene expressional profiling and proteomic profiling of EVPs from dormant and reactivated cancer cells by RNA-sequencing and LC-MS/MS.
RESULTS
We found substantial changes in gene expression and protein level in EVP. The genes with higher expression in dormant cancer cells were lipid transporter- and lipid metabolic-related genes. A total of 111 EVP proteins were upregulated in dormant cancer cells compared to those in control cells. Fifty differential expressed proteins (DEPs) were identified in EVPs from reactivated cancer cells compared to those in dormant cancer cells. Among the DEPs, we found that apolipoproteins such as APOA1 and APOE were significantly increased in dormant cancer cell-derived EVPs. Integration of EVP proteomes with transcriptional profiles of cancer cells revealed that the proteomic profiling of EVP derived from cancer cells can reflect the cellular status of cancer cells, which showed an activated lipid metabolism in dormant state.
CONCLUSION
Lipoproteins enriched in EVPs reflect the activated lipid metabolism in dormant cancer cells and may provide potential biomarkers or therapeutic targets for cisplatin-based therapy.
Identifiants
pubmed: 34520129
doi: 10.1111/1759-7714.14147
pmc: PMC8487815
doi:
Substances chimiques
Antineoplastic Agents
0
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2601-2610Informations de copyright
© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
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