DeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.

Suarez-Carmona, Meggy; Hubert, Pascale; Gonzalez, Arnaud; Duray, A; RONCARATI, Patrick; Erpicum, Charlotte; Boniver, Jacques; Castronovo, Vincenzo; Noël, Agnès; Saussez, Sven; Peulen, Olivier; Delvenne, Philippe; Herfs, Michael

doi:10.18632/oncotarget.1819

Article (Scientific journals)

DeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.

Suarez-Carmona, Meggy; Hubert, Pascale; Gonzalez, Arnaud et al.

2014 • In Oncotarget, 5 (7), p. 1856-1868

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/167713

DOI
10.18632/oncotarget.1819

PubMed
24732135

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Keywords :

p63; defensins; (lymph)angiogenesis; prognosis; squamous cell carcinoma

Abstract :

[en] Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype in tumorigenesis is still confusing. Constitutively produced or induced in inflammatory conditions, human beta-defensins (HbetaDs) are cationic peptides involved in host defenses against bacteria, viruses and fungi. Here, we investigated both the role of p63 proteins in the regulation of HbetaDs and the implication of these antimicrobial peptides in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed that DeltaNp63 proteins (alpha, beta, gamma) induce HbetaD1, 2 and 4 expression. Similar results were observed in cancer tissues and cell lines. We next demonstrated that DeltaNp63-overexpressing SCC are associated with both a poor prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we showed that HbetaDs exert a chemotactic activity for (lymphatic) endothelial cells in a CCR6-dependent manner. The ability of HbetaDs to enhance (lymph)angiogenesis in vivo was also evaluated. We observed that HbetaDs increase the vessel number and induce a significant increase in relative vascular area compared to negative control. Taken together, the results of this study suggest that DeltaNp63-regulated HbetaD could promote tumor (lymph)angiogenesis in SCC microenvironment.

Disciplines :

Biochemistry, biophysics & molecular biology
Oncology

Author, co-author :

Suarez-Carmona, Meggy ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques

Hubert, Pascale ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques

Gonzalez, Arnaud ; Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (Bologne)

Duray, A

RONCARATI, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique

Erpicum, Charlotte ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Boniver, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire

Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Saussez, Sven

More authors (3 more)

Language :

English

Title :

DeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.

Publication date :

2014

Journal title :

Oncotarget

eISSN :

1949-2553

Publisher :

Impact Journals, Albany, United States - New York

Volume :

Issue :

Pages :

1856-1868

Peer reviewed :

Peer Reviewed verified by ORBi

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since 16 May 2014

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