Publication: Spatial and phenotypic characterization of pancreatic cancer-associated fibroblasts after neoadjuvant treatment
Authors
Nielsen, Michael Friberg Bruun ; Mortensen, Michael Bau ; Sörensen, Mia Dahl ; Wirenfeldt, Martin ; Kristensen, Bjarne Winther ; Schröder, Henrik Daa ; Pfeiffer, Per ; Detlefsen, Sönke
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-201
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info:eu-repo/semantics/article
Description
Abstract
Pancreatic ductal adenocarcinoma (PC) is
characterized by a highly fibrotic desmoplastic stroma.
Subtypes of cancer-associated fibroblasts (CAFs) have
been identified in chemotherapy-naïve PC (CTN-PC),
but their precise functions are still unclear. Our
knowledge regarding the properties of CAFs in the
regressive stroma after neoadjuvant treatment (NAT) of
PC (NAT-PC) is particularly limited. We aimed to
examine the marker phenotypic properties of CAFs in
the regressive stroma of PC.
Surgical specimens from patients with CTN-PC
(n=10) and NAT-PC (n=10) were included.
Juxtatumoural, peripheral, lobular, septal, peripancreatic,
and regressive stromal compartments were manually
outlined using digital imaging analysis (DIA) for area
quantification. The compartment-specific expression of
CD271, cytoglobin, DOG-1, miR-21, osteonectin,
PDGF-Rβ, and tenascin C was evaluated by
immunohistochemistry or in situ hybridization, using
manual scoring and automated DIA.
The area fraction of the regressive stroma was
significantly higher in NAT-PC than in CTN-PC
(P=0.0002). CD271 (P<0.01), cytoglobin (P<0.05),
DOG1 (P<0.05), miR-21 (P<0.05), and tenascin C
(P<0.05) exhibited significant differences in their
expression profiles between the juxtatumoural compared
to the peripheral and regressive stroma. PDGF-Rβ
expression was significantly higher in juxtatumoural
than in peripheral CAFs (P<0.05).
Our data provide further support of the concept of
stromal heterogeneity and phenotypic different CAF
subtypes in PC. CAFs in the regressive stroma of NAT-
PC show a marker phenotype similar to some (namely,
peripheral) and different from other (namely,
juxtatumoural) previously defined CAF subtypes. It may
be hypothesized that phenotypic CAF subtypes, at least
in part, also may share functional properties. Studies
examining the precise functional characteristics of CAF
subtypes in PC are needed
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Citation
Histology and Histopathology Vol. 35, nº8 (2020)
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