New insights into hypoxia-related mechanisms involved in different microvascular patterns of bronchopulmonary carcinoids and poorly differentiated neuroendocrine carcinomas. Role of ribonuclease T2 (RNASET2) and HIF-1α.

Détails

ID Serval
serval:BIB_50F90D987DEA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
New insights into hypoxia-related mechanisms involved in different microvascular patterns of bronchopulmonary carcinoids and poorly differentiated neuroendocrine carcinomas. Role of ribonuclease T2 (RNASET2) and HIF-1α.
Périodique
Human pathology
Auteur(s)
Uccella S., La Rosa S., Scaldaferri D., Monti L., Maragliano R., Sorrenti E., Gariboldi M., Taramelli R., Sessa F., Acquati F.
ISSN
1532-8392 (Electronic)
ISSN-L
0046-8177
Statut éditorial
Publié
Date de publication
09/2018
Peer-reviewed
Oui
Volume
79
Pages
66-76
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Ribonuclease T2 (RNASET2) is a pleiotropic and polyfunctional protein, which exerts several different activities in neoplastic cells since the early steps of tumor development. Besides having an antitumorigenic activity, RNASET2 inhibits both bFGF-induced and VEGF-induced angiogenesis and has a role as a stress-response, alarmin-like, protein. In this study, we investigated RNASET2 expression in well-differentiated and poorly differentiated neuroendocrine neoplasms of the lung (Lu-NENs), which are known to show clear-cut differences in morphology, biology and clinical behavior. In addition, we explored possible relationships between RNASET2 expression and a series of immunohistochemical markers related to hypoxic stress, apoptosis, proliferation and angiogenesis. Our results showed a significantly higher expression of RNASET2, HIF-1α, and its target CA IX in poorly differentiated than in well-differentiated Lu-NENs, the former also showing higher proliferation and apoptotic rates, as well as a lower microvessel density (MVD) than the latter. Moreover, we were able to demonstrate in vitro an overexpression of RNASET2 in consequence of the activation of HIF-1α. In conclusion, we suggest that in poorly differentiated Lu-NENs, RNASET2 expression may be induced by HIF-1α, behaving as an alarmin-like molecule. In this aggressive group of cancers, which have highly deregulated proliferation pathways, RNASET2 fails to exert the growth-inhibiting effects described in other types of neoplasms. Its increased expression, however, may contribute to the typical phenotypic alterations seen in poorly differentiated Lu-NENs, such as the high apoptotic rate and the extensive necrosis, and may also enhance the low MVD observed in these neoplasms.
Mots-clé
Antigens, Neoplasm/metabolism, Apoptosis, Carbonic Anhydrase IX/metabolism, Carcinoid Tumor/blood supply, Carcinoid Tumor/enzymology, Carcinoid Tumor/pathology, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/genetics, Hypoxia-Inducible Factor 1, alpha Subunit/metabolism, Lung Neoplasms/blood supply, Lung Neoplasms/enzymology, Lung Neoplasms/pathology, MCF-7 Cells, Microvessels/metabolism, Microvessels/pathology, Necrosis, Neovascularization, Pathologic, Neuroendocrine Tumors/blood supply, Neuroendocrine Tumors/enzymology, Neuroendocrine Tumors/pathology, Ribonucleases/genetics, Ribonucleases/metabolism, Tumor Hypoxia, Tumor Microenvironment, Tumor Suppressor Proteins/genetics, Tumor Suppressor Proteins/metabolism, Alarmin, HIF-1α, Lung, Microvascular Density, Neuroendocrine Neoplasms, RNASET2
Pubmed
Web of science
Création de la notice
17/05/2018 17:10
Dernière modification de la notice
20/08/2019 14:06
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