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Proteomic characterization of microdissected breast tissue environment provides a
protein-level overview of malignant transformation
#MMPMID28058811
Braakman RB
; Stingl C
; Tilanus-Linthorst MM
; van Deurzen CH
; Timmermans MA
; Smid M
; Foekens JA
; Luider TM
; Martens JW
; Umar A
Proteomics
2017[Mar]; 17
(5
): ? PMID28058811
show ga
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.
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