Species-Specific Quantitative Proteomics Profiles of Sarcoma Patient-Derived Models Closely Reflect Their Primary Tumors.
Animals
Cell Line, Tumor
Chromatography, High Pressure Liquid
Cluster Analysis
Electrophoresis, Gel, Two-Dimensional
Extracellular Matrix
/ metabolism
Humans
Mass Spectrometry
Mice
Principal Component Analysis
Proteome
/ analysis
Proteomics
/ methods
Sarcoma
/ metabolism
Transplantation, Heterologous
patient-derived model
proteome
sarcoma
Journal
Proteomics. Clinical applications
ISSN: 1862-8354
Titre abrégé: Proteomics Clin Appl
Pays: Germany
ID NLM: 101298608
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
26
03
2019
revised:
25
07
2019
pubmed:
17
8
2019
medline:
15
5
2020
entrez:
17
8
2019
Statut:
ppublish
Résumé
The purpose is to examine whether patient-derived sarcoma models recapitulate the spectrum of sarcoma heterogeneity seen in patients. To characterize patient-derived models for functional studies, proteomic comparisons with originating sarcomas representative of three intrinsic subtypes by MS are performed. Human protein profiling is found to be retained with high fidelity in patient-derived models. The protein profiles of patient sarcoma tumors and mouse stroma are characterized by species-specific quantitative proteomics. Protein-expression levels in mouse stroma are affected by the primary human tumor. The levels of stromal proteins derived from tumors are lower in PDXs and cell lines, and some human stromal proteins are replaced by the corresponding mouse proteins in PDXs. These findings suggest that the effects of the microenvironment on drug responses may not reflect those in the primary tumor. This cross-species proteomic analysis in PDXs can potentially improve preclinical evaluation of treatment modalities and enhance the ability to predict clinical trial responses.
Identifiants
pubmed: 31419061
doi: 10.1002/prca.201900054
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1900054Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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