title: Proteomic characterization of microdissected breast tissue environment provides a protein-level overview of malignant transformation.
abstract: Both healthy and cancerous breast tissue is heterogeneous, which is a bottleneck for proteomics-based biomarker analysis, as it obscures the cellular origin of a measured protein. We therefore aimed at obtaining a protein-level interpretation of malignant transformation through global proteome analysis of a variety of laser capture microdissected cells originating from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment, and performed string analysis. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Furthermore, stroma could be clearly divided into reactive and nonreactive based on extracellular matrix disassembly proteins. We conclude that proteomics analysis of both microdissected epithelium and stroma gives an additional layer of information and more detailed insight into malignant transformation.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.|Postgraduate School of Molecular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: René B H
authors.initials: RB
authors.lastname: Braakman
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stingl
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Madeleine M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Carolien H M
authors.initials: CH
authors.lastname: van Deurzen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Mieke A M
authors.initials: MA
authors.lastname: Timmermans
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.|Postgraduate School of Molecular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.|Postgraduate School of Molecular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.|Postgraduate School of Molecular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Arzu
authors.initials: A
authors.lastname: Umar
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D042282:Microdissection; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D057188:Workflow
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins
keywords: Breast cancer; Cellular origin; Laser capture microdissection; Malignant transformation; Tissue environment