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Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis
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Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis
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Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis
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Journal Article
Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis
2013
Overview
Background:
In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI.
Methods:
We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-
Kras
G12D
mouse model of PDAC. CX3CR1 expression
in vitro
was studied by a spheroid model, and
in vivo
by syngenic mouse graft of tumour cells.
Results:
In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (
P
=0.005) and PNI (
P
=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%,
P
<0.001) and CX3CL1+ (86.8%,
P
=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (
P
=0.05). Mouse PanINs were also CX3CR1
+
and -CL1
+
.
In vitro
, cytokines significantly increased
CX3CL1
but not
CX3CR1
expression. Differently, CX3CR1 was upregulated in tumour spheroids, and
in vivo
only in well-differentiated tumours.
Conclusion:
Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - metabolism
/ Carcinoma, Pancreatic Ductal - pathology
/ Cell Differentiation - physiology
/ Chemokine CX3CL1 - biosynthesis
/ Female
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Humans
/ Ligands
/ Liver. Biliary tract. Portal circulation. Exocrine pancreas
/ Male
/ Mice
/ Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
/ Oncology
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - metabolism
/ Pancreatic Neoplasms - pathology
/ Receptors, Chemokine - biosynthesis
/ Receptors, Chemokine - genetics
/ Tumors
