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Dis Model Mech ; 13(7)2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32493768

RESUMO

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.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Proteínas de Neoplasias/metabolismo , Proteoma , Proteômica , Células Estromais/metabolismo , Espectrometria de Massas em Tandem , Animais , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Comunicação Celular , Linhagem Celular Tumoral , Cromatografia Líquida , Bases de Dados de Proteínas , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos SCID , Células NIH 3T3 , Transplante de Neoplasias , Especificidade da Espécie , Células Estromais/patologia , Microambiente Tumoral
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