Proteomic characterization of microdissected breast tissue environment provides a protein‐level overview of malignant transformation

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 analy...

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Bibliographic Details
Published in:Proteomics (Weinheim) 2017-03, Vol.17 (5), p.np-n/a
Main Authors: Braakman, René B. H., Stingl, Christoph, Tilanus‐Linthorst, Madeleine M. A., van Deurzen, Carolien H. M., Timmermans, Mieke A. M., Smid, Marcel, Foekens, John A., Luider, Theo M., Martens, John W. M., Umar, Arzu
Format: Article
Language:English
Subjects:
Benign
Biomarkers
Biomarkers, Tumor - analysis
Biomarkers, Tumor - metabolism
Biomedicine
Breast
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Cell adhesion
Cell adhesion & migration
Cellular origin
Dismantling
Energy metabolism
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - pathology
Epithelium
Extracellular matrix
Female
Genetic transformation
Humans
Immune system
Laser capture microdissection
Malignant transformation
Mass Spectrometry - methods
Metabolism
Microdissection
Proteins
Proteins - analysis
Proteins - metabolism
Proteomics
Proteomics - methods
Stroma
Stromal Cells - metabolism
Stromal Cells - pathology
Tissue environment
Tissues
Workflow
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Summary: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.
ISSN:1615-9853
1615-9861
DOI:10.1002/pmic.201600213