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CD26 Is Differentially Expressed throughout the Life Cycle of Infantile Hemangiomas and Characterizes the Proliferative Phase

Authors :
Bruno Lorusso
Antonella Nogara
Rodanthi Fioretzaki
Emilia Corradini
Roberta Bove
Giovanni Roti
Andrea Gherli
Anna Montanaro
Gregorio Monica
Filippo Cavazzini
Sabrina Bonomini
Gallia Graiani
Enrico Maria Silini
Letizia Gnetti
Francesco Paolo Pilato
Giuseppe Cerasoli
Federico Quaini
Costanza Anna Maria Lagrasta
Source :
International Journal of Molecular Sciences, Vol 25, Iss 18, p 9760 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5–10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4–7 years). The mechanisms underlying this neoplastic disease still remain uncovered. Twenty-seven IH tissue specimens (15 proliferative and 12 involuting) were subjected to hematoxylin and eosin staining and a panel of diagnostic markers by immunohistochemistry. WT1, nestin, CD133, and CD26 were also analyzed. Moreover, CD31pos/CD26pos proliferative hemangioma–derived endothelial cells (Hem-ECs) were freshly isolated, exposed to vildagliptin (a DPP-IV/CD26 inhibitor), and tested for cell survival and proliferation by MTT assay, FACS analysis, and Western blot assay. All IHs displayed positive CD31, GLUT1, WT1, and nestin immunostaining but were negative for D2-40. Increased endothelial cell proliferation in IH samples was documented by ki67 labeling. All endothelia of proliferative IHs were positive for CD26 (100%), while only 10 expressed CD133 (66.6%). Surprisingly, seven involuting IH samples (58.3%) exhibited coexisting proliferative and involuting aspects in the same hemangiomatous lesion. Importantly, proliferative areas were characterized by CD26 immunolabeling, at variance from involuting sites that were always CD26 negative. Finally, in vitro DPP-IV pharmacological inhibition by vildagliptin significantly reduced Hem-ECs proliferation through the modulation of ki67 and induced cell cycle arrest associated with the upregulation of p21 protein expression. Taken together, our findings suggest that CD26 might represent a reliable biomarker to detect proliferative sites and unveil non-regressive IHs after a 12-month life cycle.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
25
Issue :
18
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.20497f1938b04f179f77d8e2b9a13a19
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms25189760