Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets.
JCI Insight
; 5(15)2020 08 06.
Article
in En
| MEDLINE
| ID: mdl-32634123
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a relative paucity of cancer cells that are surrounded by an abundance of nontumor cells and extracellular matrix, known as stroma. The interaction between stroma and cancer cells contributes to poor outcome, but how proteins from these individual compartments drive aggressive tumor behavior is not known. Here, we report the proteomic analysis of laser-capture microdissected (LCM) PDAC samples. We isolated stroma, tumor, and bulk samples from a cohort with long- and short-term survivors. Compartment-specific proteins were measured by mass spectrometry, yielding what we believe to be the largest PDAC proteome landscape to date. These analyses revealed that, in bulk analysis, tumor-derived proteins were typically masked and that LCM was required to reveal biology and prognostic markers. We validated tumor CALB2 and stromal COL11A1 expression as compartment-specific prognostic markers. We identified and functionally addressed the contributions of the tumor cell receptor EPHA2 to tumor cell viability and motility, underscoring the value of compartment-specific protein analysis in PDAC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Biomarkers, Tumor
/
Stromal Cells
/
Proteome
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Carcinoma, Pancreatic Ductal
/
Extracellular Matrix
Type of study:
Prognostic_studies
Limits:
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
JCI Insight
Year:
2020
Document type:
Article