title: ΔNp63 isoform-mediated β-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.
abstract: 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 (HβDs) 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 HβDs and the implication of these antimicrobial peptides in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed that ΔNp63 proteins (α, β, γ) induce HβD1, 2 and 4 expression. Similar results were observed in cancer tissues and cell lines. We next demonstrated that ΔNp63-overexpressing SCC are associated with both a poor prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we showed that HβDs exert a chemotactic activity for (lymphatic) endothelial cells in a CCR6-dependent manner. The ability of HβDs to enhance (lymph)angiogenesis in vivo was also evaluated. We observed that HβDs 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 ΔNp63-regulated HβD could promote tumor (lymph)angiogenesis in SCC microenvironment.
authors.affiliation: Laboratory of Experimental Pathology, GIGA-Cancer, University of Liege, Liege, Belgium.
authors.forename: Meggy
authors.initials: M
authors.lastname: Suarez-Carmona
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Anaelle
authors.initials: A
authors.lastname: Duray
authors.forename: Patrick
authors.initials: P
authors.lastname: Roncarati
authors.forename: Charlotte
authors.initials: C
authors.lastname: Erpicum
authors.forename: Jacques
authors.initials: J
authors.lastname: Boniver
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
authors.forename: Agnès
authors.initials: A
authors.lastname: Noel
authors.forename: Sven
authors.initials: S
authors.lastname: Saussez
authors.forename: Olivier
authors.initials: O
authors.lastname: Peulen
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Michael
authors.initials: M
authors.lastname: Herfs
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D002633:Chemotaxis; D042783:Endothelial Cells; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes; D042583:Lymphangiogenesis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D054399:Receptors, CCR6 / Q000378:metabolism; D015996:Survival Rate; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D059016:Tumor Microenvironment; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000235:genetics*; D023083:beta-Defensins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054399:Receptors, CCR6; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D023083:beta-Defensins
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