Comparative proteomic analysis in human and canine breast cancer cell line: identification of proteins linked to lipid dynamics and functions

Breast cancer is the most common neoplasia worldwide in humans, and one of the most common in dogs. There are multiple similarities at the clinical, hormonal and molecular levels between both species, suggesting the dog could be an optimal oncological model. Alterations in lipid homeostasis and/or metabolism are necessary to acquire the hallmarks of cancer. This study focused on the identification of proteomic similarities between human and canine BC cell lines, with an emphasis on proteins related to various lipid functionalities. Three human cell lines, 184B5 – non tumoral –, MCF-7 – Luminal A – and MDA-MB231 – triple-negative –, and two canine triple-negative cell lines, CMT-U27 and IPC-366, were analysed by LC-MS/MS. A total of 721 orthologous proteins were identified, where nearly 22% of them showed significant differences (up or down) in the four tumour lines compared to 184B5 cell line, with a minimum fold change of 30%. Likewise, approximately 14% of the orthologous proteins presented significant differences with a minimum FC of 30% specific to the triple-negative phenotype, regardless of the species. Functional analysis using KEGG and Metascape revealed alterations in proteins related to proliferation, membrane trafficking and lipid metabolism, among others, in both species. This study aims to reinforce the potential of using canine models in oncology for the search for possible diagnostic and monitoring biomarker or therapeutic targets.