A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts

• Published in: Disease models & mechanisms Vol. 13; no. 7
• Main Authors: Krasny, Lukas, Bland, Philip, Burns, Jessica, Lima, Nadia Carvalho, Harrison, Peter T, Pacini, Laura, Elms, Mark L, Ning, Jian, Martinez, Victor Garcia, Yu, Yi-Ru, Acton, Sophie E, Ho, Ping-Chih, Calvo, Fernando, Swain, Amanda, Howard, Beatrice A, Natrajan, Rachael C, Huang, Paul H
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 14.07.2020; The Company of Biologists
• Subjects: Animals; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - pathology; Cell Communication; Cell Line, Tumor; Chromatography; Chromatography, Liquid; Databases, Protein; Datasets; dcis; Experiments; Female; Heterografts; Humans; Laboratories; Libraries; Male; Mass spectrometry; Medical research; Mice; Mice, Inbred C57BL; Mice, Nude; Mice, SCID; mouse; Mouse Models; Neoplasm Proteins - metabolism; Neoplasm Transplantation; NIH 3T3 Cells; Peptides; Proteins; Proteome; Proteomics; Reproducibility; Resource; Retention; Scientific imaging; Software; Species Specificity; Stromal Cells - metabolism; Stromal Cells - pathology; swath-ms; Tandem Mass Spectrometry; Tumor Microenvironment; Xenografts; Mouse; DCIS; Proteomics; Xenografts; SWATH-MS; Breast cancer; Mass spectrometry
• ISSN: 1754-8403; 1754-8411; 1754-8411
• DOI: 10.1242/dmm.044586

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 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.