Proteomics

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Proteomic characterization of microdissected epithelium, tumor cells, and stroma from breast tissues


ABSTRACT: Tissue of the breast is heterogeneous, consisting of a variety of cell types and connective tissue. This heterogeneity is also present in breast tumors and will complicate proteomic analysis, as it is not always clear whether a signal originates from the stromal environment, from normal epithelial or tumor cells. Here we microdissected a variety of cell types and stroma from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment. 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. Although this heterogeneity complicated detection of differentially abundant proteins, several markers were exclusively detected in stroma. However, as heterogeneity in the stroma is more difficult to be reduced through microdissection, comparative analysis was most informative in microdissected cells of epithelial origin, and provided a relatively complete picture of malignant transformations.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Mammary Gland

DISEASE(S): Breast Cancer

SUBMITTER: Rene Braakman  

LAB HEAD: John W. M. Martens

PROVIDER: PXD003632 | Pride | 2017-01-11

REPOSITORIES: Pride

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Publications

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

Braakman René B H RB   Stingl Christoph C   Tilanus-Linthorst Madeleine M A MM   van Deurzen Carolien H M CH   Timmermans Mieke A M MA   Smid Marcel M   Foekens John A JA   Luider Theo M TM   Martens John W M JW   Umar Arzu A  

Proteomics 20170301 5


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 orig  ...[more]

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