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

Disease Models & Mechanisms

Yi-Ru Yu¹  Ping-Chih Ho¹  Paul H. Huang²  Nadia Carvalho Lima²  Jessica Burns²  Peter T. Harrison²  Lukas Krasny²  Mark L. Elms²  Laura Pacini²  Sophie E. Acton³  Victor Garcia Martinez³  Philip Bland⁴  Rachael C. Natrajan⁴  Beatrice A. Howard⁴  Fernando Calvo⁵  Jian Ning⁶  Amanda Swain⁶ 

[1] Department of Oncology, University of Lausanne, Lausanne CH-1066, Switzerland;Division of Molecular Pathology, The Institute of Cancer Research, London SW3 6JB, UK;Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London WC1E 6BT, London, UK;The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK;The Tumour Microenvironment Team, Institute of Biomedicine and Biotechnology of Cantabria, Santander 39011, Spain;Tumour Profiling Unit, The Institute of Cancer Research, London SW3 6JB, UK;

关键词: mass spectrometry;    swath-ms;    proteomics;    mouse;    xenografts;    dcis;    breast cancer;   

DOI  :  10.1242/dmm.044586

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown