Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of alpha 2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM.

Polysialic acid sustains the hypoxia-induced migration and undifferentiated state of human glioblastoma cells / Rosa, Paolo; Scibetta, Sofia; Pepe, Giuseppe; Mangino, Giorgio; Capocci, Luca; Moons, Sam J; Boltje, Thomas J; Fazi, Francesco; Petrozza, Vincenzo; Di Pardo, Alba; Maglione, Vittorio; Calogero, Antonella. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:17(2022), pp. 1-22. [10.3390/ijms23179563]

Polysialic acid sustains the hypoxia-induced migration and undifferentiated state of human glioblastoma cells

Rosa, Paolo
Primo
;
Scibetta, Sofia
Secondo
;
Mangino, Giorgio;Fazi, Francesco;Petrozza, Vincenzo;Di Pardo, Alba;Calogero, Antonella
Ultimo
2022

Abstract

Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of alpha 2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM.
2022
differentiation; glioblastoma; hypoxia; migration; polysialic acid
01 Pubblicazione su rivista::01a Articolo in rivista
Polysialic acid sustains the hypoxia-induced migration and undifferentiated state of human glioblastoma cells / Rosa, Paolo; Scibetta, Sofia; Pepe, Giuseppe; Mangino, Giorgio; Capocci, Luca; Moons, Sam J; Boltje, Thomas J; Fazi, Francesco; Petrozza, Vincenzo; Di Pardo, Alba; Maglione, Vittorio; Calogero, Antonella. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:17(2022), pp. 1-22. [10.3390/ijms23179563]
File allegati a questo prodotto
File Dimensione Formato  
Rosa_Polysialic_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 4.98 MB
Formato Adobe PDF
4.98 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1655264
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact