A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts.
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Authors
Krasny, L
Bland, P
Burns, J
Lima, NC
Harrison, PT
Pacini, L
Elms, ML
Ning, J
Martinez, VG
Yu, Y-R
Acton, SE
Ho, P-C
Calvo, F
Swain, A
Howard, BA
Natrajan, RC
Huang, PH
Bland, P
Burns, J
Lima, NC
Harrison, PT
Pacini, L
Elms, ML
Ning, J
Martinez, VG
Yu, Y-R
Acton, SE
Ho, P-C
Calvo, F
Swain, A
Howard, BA
Natrajan, RC
Huang, PH
Document Type
Journal Article
Date
2020-06-03
Date Accepted
2020-05-20
Abstract
SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high sequence similarity between mouse and human proteins, facilitating the study of host microenvironment-tumour interactions from 'bulk tumour' measurements. We apply the XenoSWATH pipeline to characterize an intraductal xenograft model of breast ductal carcinoma in situ and uncover complex regulation consistent with stromal reprogramming, where the modulation of cell migration pathways is not restricted to tumour cells but also operates in the mouse stroma upon progression to invasive disease. MouseRefSWATH and XenoSWATH open new opportunities for in-depth and reproducible proteomic assessment to address wide-ranging biological questions involving this important model organism.
Citation
Disease models & mechanisms, 2020, 13 (7)
Source Title
Publisher
COMPANY BIOLOGISTS LTD
ISSN
1754-8403
eISSN
1754-8411
Research Team
Endocrine control mechanisms
Development & Cancer
Functional Genomics
Molecular and Systems Oncology
Development & Cancer
Functional Genomics
Molecular and Systems Oncology