Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression.

Biomolecules
Salvatore PanzaSebastiano Andò

Abstract

Glioblastoma multiforme (GBM) is the most malignant form of glioma, which represents one of the commonly occurring tumors of the central nervous system. Despite the continuous development of new clinical therapies against this malignancy, it still remains a deadly disease with very poor prognosis. Here, we demonstrated the existence of a biologically active interaction between leptin and Notch signaling pathways that sustains GBM development and progression. We found that the expression of leptin and its receptors was significantly higher in human glioblastoma cells, U-87 MG and T98G, than in a normal human glial cell line, SVG p12, and that activation of leptin signaling induced growth and motility in GBM cells. Interestingly, flow cytometry and real-time RT-PCR assays revealed that GBM cells, grown as neurospheres, displayed stem cell-like properties (CD133+) along with an enhanced expression of leptin receptors. Leptin treatment significantly increased the neurosphere forming efficiency, self-renewal capacity, and mRNA expression levels of the stemness markers CD133, Nestin, SOX2, and GFAP. Mechanistically, we evidenced a leptin-mediated upregulation of Notch 1 receptor and the activation of its downstream effectors and targ...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Tsung-Chieh Lin, Michael Hsiao
May 1, 2021·International Journal of Molecular Sciences·Karolina WołodkoAntónio Galvão
May 1, 2021·International Journal of Molecular Sciences·Vincenzo MatteiClaudio Festuccia
Aug 7, 2021·Biomolecules·Marianna GrecoAntonella Leggio

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Methods Mentioned

BETA
surgical resection
Assay
Transfection

Software Mentioned

ELDA
GraphPad
WinDI
- Prism7
Scion Image

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