Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-10

AUTHORS

G Celesti, G Di Caro, P Bianchi, F Grizzi, F Marchesi, G Basso, D Rahal, G Delconte, M Catalano, P Cappello, M Roncalli, A Zerbi, M Montorsi, F Novelli, A Mantovani, P Allavena, A Malesci, L Laghi

ABSTRACT

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. More... »

PAGES

2424

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2013.565

DOI

http://dx.doi.org/10.1038/bjc.2013.565

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048174357

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24084767


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