Ectopic nerve growth factor prevents proliferation in glioma cells by senescence induction

Antonio Ruggiero, Daniela Meco, Linda Melotti, Riccardo Riccardi

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

1 Citazioni (Scopus)

Abstract

OBJECTIVE: The neurotrophin nerve growth factor (NGF) affects survival, regulation and differentiation of both central and peripheral nervous system neurons. NGF exerts its effects primarily through tropomyosin receptor kinase A (TrkA), inducing a cascade of tyrosine kinase-initiated responses. In spite of its importance, the general behavior of NGF looks contradictory: its effects can be both stimulatory and inhibitory. The present study aims to explore the molecular mechanisms induced by NGF in glioma cancer cells. METHODS: The effects of NGF were investigated in high grade glioma and low grade pediatric glioma (PLGG) cell lines through comparative studies. In particular, we investigated TrkA-mediated cellular pathways, molecular signaling, proliferation, cell cycle and cellular senescence. RESULTS: We found that exposure of PLGG cells to NGF produced stable growth arrest with the features of a senescence phenotype but without the expression of anti-poly(ADP-ribose) polymerase cleavage, a marker of apoptosis. Moreover, NGF treatment promoted the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling. In addition, K252a, a TrkA inhibitor, significantly reduced the phosphorylation of the aforementioned signaling pathways, suggesting that NGF-activated ERK1/2 and AKT signaling take place downstream of TrkA-neurotrophin interaction. CONCLUSIONS: These findings provide the first evidence that NGF can induce senescence of PLGG cells in a receptor-mediated fashion, thus supporting the hypothesis that in the clinical setting NGF might be beneficial to pediatric glioma patients.
Lingua originaleEnglish
pagine (da-a)6820-6830
Numero di pagine11
RivistaJournal of Cellular Physiology
Volume234
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • cellular senescence
  • glioma cell lines
  • nerve growth factor (NGF)
  • neurotrophin

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