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-KrasG12D 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

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis / 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. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - 109:9(2013 Oct 29), pp. 2424-2433.

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis

G. Celesti;G. Di Caro;F. Marchesi;G. Basso;G. Delconte;M. Catalano;M. Roncalli;M. Montorsi;A. Mantovani;A. Malesci;
2013-10-29

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-KrasG12D 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
pancreatic cancer; CX3CR1; perineural invasion
Settore MED/12 - Gastroenterologia
Settore MED/18 - Chirurgia Generale
Settore MED/08 - Anatomia Patologica
Settore MED/04 - Patologia Generale
Settore MED/09 - Medicina Interna
1-ott-2013
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/226180
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