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Cancer cell line-specific protein profiles in extracellular vesicles identified by proteomics

Extracellular vesicles (EVs), are important for intercellular communication in both physiological and pathological processes. To explore the potential of cancer derived EVs as disease biomarkers for diagnosis, monitoring, and treatment decision, it is necessary to thoroughly characterize their biomo...

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Published in:PloS one 2020-09, Vol.15 (9), p.e0238591
Main Authors: Guerreiro, Eduarda M, Øvstebø, Reidun, Thiede, Bernd, Costea, Daniela Elena, Søland, Tine M, Kanli Galtung, Hilde
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cited_by cdi_FETCH-LOGICAL-c716t-83acfd694b1a186be1a3ae8b08188ffb86cbd66978d952d56f7b59c6829919d83
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creator Guerreiro, Eduarda M
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description Extracellular vesicles (EVs), are important for intercellular communication in both physiological and pathological processes. To explore the potential of cancer derived EVs as disease biomarkers for diagnosis, monitoring, and treatment decision, it is necessary to thoroughly characterize their biomolecular content. The aim of the study was to characterize and compare the protein content of EVs derived from three different cancer cell lines in search of a specific molecular signature, with emphasis on proteins related to the carcinogenic process. Oral squamous cell carcinoma (OSCC), pancreatic ductal adenocarcinoma (PDAC) and melanoma brain metastasis cell lines were cultured in CELLine AD1000 flasks. EVs were isolated by ultrafiltration and size-exclusion chromatography and characterized. Next, the isolated EVs underwent liquid chromatography-mass spectrometry (LC-MS) analysis for protein identification. Functional enrichment analysis was performed for a more general overview of the biological processes involved. More than 600 different proteins were identified in EVs from each particular cell line. Here, 14%, 10%, and 24% of the identified proteins were unique in OSCC, PDAC, and melanoma vesicles, respectively. A specific protein profile was discovered for each cell line, e.g., EGFR in OSCC, Muc5AC in PDAC, and FN1 in melanoma vesicles. Nevertheless, 25% of all the identified proteins were common to all cell lines. Functional enrichment analysis linked the proteins in each data set to biological processes such as "biological adhesion", "cell motility", and "cellular component biogenesis". EV proteomics discovered cancer-specific protein profiles, with proteins involved in processes promoting tumor progression. In addition, the biological processes associated to the melanoma-derived EVs were distinct from the ones linked to the EVs isolated from OSCC and PDAC. The malignancy specific biomolecular cues in EVs may have potential applications as diagnostic biomarkers and in therapy.
doi_str_mv 10.1371/journal.pone.0238591
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Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guerreiro, Eduarda M</au><au>Øvstebø, Reidun</au><au>Thiede, Bernd</au><au>Costea, Daniela Elena</au><au>Søland, Tine M</au><au>Kanli Galtung, Hilde</au><au>Horowitz, Arie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer cell line-specific protein profiles in extracellular vesicles identified by proteomics</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-09-04</date><risdate>2020</risdate><volume>15</volume><issue>9</issue><spage>e0238591</spage><pages>e0238591-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Extracellular vesicles (EVs), are important for intercellular communication in both physiological and pathological processes. To explore the potential of cancer derived EVs as disease biomarkers for diagnosis, monitoring, and treatment decision, it is necessary to thoroughly characterize their biomolecular content. The aim of the study was to characterize and compare the protein content of EVs derived from three different cancer cell lines in search of a specific molecular signature, with emphasis on proteins related to the carcinogenic process. Oral squamous cell carcinoma (OSCC), pancreatic ductal adenocarcinoma (PDAC) and melanoma brain metastasis cell lines were cultured in CELLine AD1000 flasks. EVs were isolated by ultrafiltration and size-exclusion chromatography and characterized. Next, the isolated EVs underwent liquid chromatography-mass spectrometry (LC-MS) analysis for protein identification. Functional enrichment analysis was performed for a more general overview of the biological processes involved. More than 600 different proteins were identified in EVs from each particular cell line. Here, 14%, 10%, and 24% of the identified proteins were unique in OSCC, PDAC, and melanoma vesicles, respectively. A specific protein profile was discovered for each cell line, e.g., EGFR in OSCC, Muc5AC in PDAC, and FN1 in melanoma vesicles. Nevertheless, 25% of all the identified proteins were common to all cell lines. Functional enrichment analysis linked the proteins in each data set to biological processes such as "biological adhesion", "cell motility", and "cellular component biogenesis". EV proteomics discovered cancer-specific protein profiles, with proteins involved in processes promoting tumor progression. In addition, the biological processes associated to the melanoma-derived EVs were distinct from the ones linked to the EVs isolated from OSCC and PDAC. The malignancy specific biomolecular cues in EVs may have potential applications as diagnostic biomarkers and in therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32886718</pmid><doi>10.1371/journal.pone.0238591</doi><tpages>e0238591</tpages><orcidid>https://orcid.org/0000-0001-7825-3540</orcidid><oa>free_for_read</oa></addata></record>
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source NORA - Norwegian Open Research Archives; Publicly Available Content Database; PubMed
subjects Adenocarcinoma
Biological activity
Biology
Biology and Life Sciences
Biomarkers
Biomarkers, Tumor - analysis
Biosynthesis
Biotechnology
Blood
Brain Neoplasms - chemistry
Brain Neoplasms - diagnosis
Brain Neoplasms - pathology
Brain Neoplasms - secondary
Cancer
Cancer cells
Cancer research
Carcinogens
Carcinoma, Pancreatic Ductal - chemistry
Carcinoma, Pancreatic Ductal - diagnosis
Carcinoma, Pancreatic Ductal - pathology
Carcinoma, Squamous Cell - chemistry
Carcinoma, Squamous Cell - diagnosis
Carcinoma, Squamous Cell - pathology
Cell culture
Cell Line, Tumor
Cell signaling
Chromatography
Decision making
Dentistry
Development and progression
Diagnosis
Diagnostic software
Diagnostic systems
Disease
Epidermal growth factor receptors
Extracellular vesicles
Extracellular Vesicles - chemistry
Extracellular Vesicles - pathology
Flasks
Health aspects
Hospitals
Humans
Liquid chromatography
Malignancy
Mass Spectrometry
Mass spectroscopy
Medical treatment
Medicine and Health Sciences
Melanoma
Melanoma - chemistry
Melanoma - diagnosis
Melanoma - pathology
Metastases
Metastasis
Mouth cancer
Mouth Neoplasms - chemistry
Mouth Neoplasms - diagnosis
Mouth Neoplasms - pathology
Neoplasms - chemistry
Neoplasms - diagnosis
Neoplasms - pathology
Ontology
Oral squamous cell carcinoma
Organelles
Pancreas
Pancreatic cancer
Pancreatic carcinoma
Pancreatic Neoplasms - chemistry
Pancreatic Neoplasms - diagnosis
Pancreatic Neoplasms - pathology
Pathology
Physiological aspects
Proteins
Proteins - analysis
Proteomics
Research and Analysis Methods
Scientific imaging
Size exclusion chromatography
Skin cancer
Squamous cell carcinoma
Supervision
Tumor cell lines
Ultrafiltration
Vesicles
title Cancer cell line-specific protein profiles in extracellular vesicles identified by proteomics
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