My project aimed at unveiling new molecular aspects involved in glioma progression. Since glutamate homeostasis deregulation seems to play a key role in glioblastoma (GBM) aggressiveness, the first part of the project was designed to deepen the role of the mitochondrial enzyme GLUD2 (glutamate dehydrogenase 2), which resulted differentially expressed between GBM patients with different recurrence-free survival after first surgery. I took advantage of Danio rerio embryos as an in vivo model to figure out GLUD2 possible function in regulating cell proliferation and survival, in order to evaluate its potential involvement in tumor growth. The second part of the project focused on another distinctive hallmark of gliomas, the infiltrative activity, which makes tumor complete surgical resection almost impossible. Given the urgent need of innovative therapeutic strategies, I tried to unveil new molecular mechanisms responsible of gliomas invasive nature. To this purpose, I investigated the role of PDGF-B in cell migration, since its up-regulation seemed to confer in vivo infiltrating properties on glioma tumor cells, exploiting Xenopus laevis neural crest cells (NCC) for their similarity to metastatic cancer cells. This model gave me the opportunity to achieve the final goal of my research, thus the possibility to discover new molecules involved in cell migration modulated downstream of PDGF-B signaling, paving the way towards the identification of new molecular therapeutic targets.

Danio rerio and Xenopus laevis embryos: alternative and valuable models to unveil new molecular mechanisms involved in glioma progression.

CORSINOVI, DEBORA
2018

Abstract

My project aimed at unveiling new molecular aspects involved in glioma progression. Since glutamate homeostasis deregulation seems to play a key role in glioblastoma (GBM) aggressiveness, the first part of the project was designed to deepen the role of the mitochondrial enzyme GLUD2 (glutamate dehydrogenase 2), which resulted differentially expressed between GBM patients with different recurrence-free survival after first surgery. I took advantage of Danio rerio embryos as an in vivo model to figure out GLUD2 possible function in regulating cell proliferation and survival, in order to evaluate its potential involvement in tumor growth. The second part of the project focused on another distinctive hallmark of gliomas, the infiltrative activity, which makes tumor complete surgical resection almost impossible. Given the urgent need of innovative therapeutic strategies, I tried to unveil new molecular mechanisms responsible of gliomas invasive nature. To this purpose, I investigated the role of PDGF-B in cell migration, since its up-regulation seemed to confer in vivo infiltrating properties on glioma tumor cells, exploiting Xenopus laevis neural crest cells (NCC) for their similarity to metastatic cancer cells. This model gave me the opportunity to achieve the final goal of my research, thus the possibility to discover new molecules involved in cell migration modulated downstream of PDGF-B signaling, paving the way towards the identification of new molecular therapeutic targets.
10-dic-2018
Italiano
glioma
GLUD2
neural crest
PDGF-B
Xenopus
Zebrafish
Naccarato, Antonio Giuseppe
File in questo prodotto:
File Dimensione Formato  
PhD_Thesis_Debora_Corsinovi.pdf

accesso aperto

Licenza: Tutti i diritti riservati
Dimensione 9.53 MB
Formato Adobe PDF
9.53 MB Adobe PDF Visualizza/Apri
Relazione_attivit_svolte_Debora_Corsinovi.pdf

accesso aperto

Licenza: Tutti i diritti riservati
Dimensione 407.25 kB
Formato Adobe PDF
407.25 kB Adobe PDF Visualizza/Apri

I documenti in UNITESI 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/20.500.14242/133590
Il codice NBN di questa tesi è URN:NBN:IT:UNIPI-133590