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Tesi etd-03022017-161436


Thesis type
Tesi di dottorato di ricerca
Author
GIANNETTI, KETY
URN
etd-03022017-161436
Title
Use of Xenopus laevis Neural Crest Cells to study the role of PDGF-B in gliomas tumor progression
Settore scientifico disciplinare
BIO/06
Corso di studi
BIOLOGIA
Commissione
tutor Prof.ssa Ori, Michela
Parole chiave
  • glioma
  • neural crest cells
  • pdgf-b
  • Xenopus laevis
Data inizio appello
15/03/2017;
Consultabilità
parziale
Data di rilascio
15/03/2087
Riassunto analitico
Gliomas are the most common primary tumours of the central nervous system; one of their major features is the ability of individual cells to infiltrate the brain parenchyma, which renders these tumours also the most aggressive. Evidences gained from studies on animal models have firmly established a causal connection between aberrant PDGF-B signalling and the formation of some gliomas. The aim of my project is to unravel the mechanisms underlying PDGF-B driven gliomagenesis and tumour progression, especially focusing on alteration of motility and migration. For this purpose, I used the animal model Xenopus laevis and in particular I focused on Neural Crest Cells (NCC), considering the many similarities shared by this population with cancer cells.<br>I demonstrated that over-expression of human PDGF-B in Xenopus embryos, obtained by mRNA microinjection, can alter NCC behaviour in terms of migration and streams segregation, validating the system. I then analysed, in PDGF-B injected embryos, the expression of some of the key players known to regulate NCC development such as: Cadherins, Chemokines and their receptors, Neuropilins and Semaphorins and Wnt/PCP pathway members. The results obtained highlighted a significant down-regulation of neuropilin-2 and of wnt11, a Wnt/PCP pathway member, suggesting for the first time a link between their expression and the PDGF signalling. The discovery of these new putative targets of the PDGF-B signalling pathway opens new possible lines of investigations aimed to identify alternative therapeutic approaches for glioma treatment. <br>Interestingly, I also evidenced that the gene expression pattern of Xenopus pdgf-b during embryogenesis relies in domains close to NCC, suggesting a possible physiological role for it in NCC development. In this regard, I deeper characterised the spatial and temporal expression profile of Pdgf-b during Xenopus embryogenesis and I performed loss of function experiments that showed how NCC migration is affected after pdgf-b down-regulation. Furthermore, with an in vivo chemotaxis assay, I observed that PDGF-BB can act as a chemoattractant for NCC in vivo, suggesting a putative chemotactic role for it and strengthening the hypothesis that this growth factor might play a physiological role in NCC migration. <br>
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