Role of differentiation in glioblastoma invasion

Justin Vareecal Joseph

Role of differentiation in glioblastoma invasion

Vertaalde titel van de bijdrage: De rol van differentiatie bij het invasieve gedrag van glioblastomen (hersentumoren)

Justin Vareecal Joseph

Onderzoeksoutput

3316 Downloads (Pure)

Samenvatting

Glioblastoma (GBM) is de meest agressieve hersentumor en diffuse infiltratie in het normale hersenweefsel is
een van de hoofdoorzaken van een slechte prognose, aangezien volledige chirurgische verwijdering hierdoor
vrijwel onmogelijk is. Het belangrijkste doel van het in dit proefschrift beschreven onderzoek was om de
mogelijke betrokkenheid van differentiatie van GBM cellen in relatie tot het invasieve gedrag van GBM
te onderzoeken. Ten eerste, hebben we ontdekt dat twee belangrijke micromilieu factoren bij GBM, namelijk
TGF-β en hypoxie, mesenchymale transdifferentiatie in GBM cellen kan induceren waardoor tegelijkertijd hun
invasive gedrag verhoogd wordt. De transcriptiefactor ZEB1 bleek een essentiële factor te zijn bij de regulatie
van dit proces. Ten tweede, is de relatie tussen de differentiatie toestand van GBM cellen en hun invasieve
gedrag onderzocht. We vonden dat gedifferentieerde GBM cellen een sterker invasief gedrag
vertoonde dan ongedifferentieerde GBM (stam) cellen. Verder toonden we aan dat gedifferentieerde cellen ook
kunnen de-differentiëren onder invloed van omgevingsfactoren tot cellen met de eigenschappen van
stamcellen welke verhoogde tumorvormende eigenschappen hebben. Deze nieuwe bevindingen laten zien dat
mesenchymale transitie en differentiatie het invasieve gedrag van GBM cellen verhogen. Remming van de
gevonden moleculaire mechanismen bieden nieuwe mogelijkheden voor het ontwikkelen van nieuwe therapieën
om het infiltrerende gedrag van deze agressieve hersentumoren te verminderen.

Vertaalde titel van de bijdrage	De rol van differentiatie bij het invasieve gedrag van glioblastomen (hersentumoren)
Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Kruyt, Frank, Supervisor den Dunnen, Wilfred, Co-supervisor
Datum van toekenning	11-mei-2015
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-90-367-7856-5
Elektronische ISBN's	978-90-367-7855-8
Status	Published - 2015

Toegang tot document

Title and contentsFinal publisher's version, 202 KB
Chapter 1Final publisher's version, 237 KB
Chapter 3Final publisher's version, 1,01 MB
Chapter 4Final publisher's version, 17,1 MB
Chapter 5Final publisher's version, 4,65 MB
Chapter 6Final publisher's version, 1,18 MB
Chapter 7Final publisher's version, 6,45 MB
Chapter 8Final publisher's version, 3,47 MB
Chapter 9Final publisher's version, 399 KB
Chapter 10Final publisher's version, 235 KB
AppendicesFinal publisher's version, 259 KB
Complete dissertationFinal publisher's version, 43 MB
PropostitionsFinal publisher's version, 483 KB

Handle.net

Permanente koppeling

Citeer dit

@phdthesis{580e94744b89499993e8d7f7b865e3b3,

title = "Role of differentiation in glioblastoma invasion",

abstract = "Glioblastoma (GBM) is the most aggressive brain tumor and its diffuse infiltration in to the normal brain tissue is one of the main causes for poor prognosis, making complete surgical removal virtually impossible. The main aim of the research described in this thesis was to investigate the possible involvement of differentiation of GBM cells in the invasive behavior of GBM. First, we discovered that two important microenvironmental factors in GBM, namely TGF-β and hypoxia, induced a mesenchymal transdifferentiation in GBM cells thereby enhancing its invasive potential. The transcription factors ZEB1 was identified as a critical regulator of this process. Second, the involvement of the differentiation state in GBM in determining their invasive capacity was examined. Interestingly, differentiated GBM cells appeared more invasive than the undifferentiated GBM (stem) cells. Further we showed that differentiated cells could also revert back and gain many of the properties associated with stem cells hence sustaining tumorigenicity. These novel findings indicate that mesenchymal transition and differentiation enhance the invasive capacity of GBM cells. Inhibition of the identified pathways contribute to heterogeneity and provide potential therapeutic targets to reduce the infiltrating behavior of this aggressive and lethal brain tumor.",

author = "\{Vareecal Joseph\}, Justin",

year = "2015",

language = "English",

isbn = "978-90-367-7856-5",

publisher = "University of Groningen",

school = "University of Groningen",

}

TY - BOOK

T1 - Role of differentiation in glioblastoma invasion

AU - Vareecal Joseph, Justin

PY - 2015

Y1 - 2015

N2 - Glioblastoma (GBM) is the most aggressive brain tumor and its diffuse infiltration in to the normal brain tissue is one of the main causes for poor prognosis, making complete surgical removal virtually impossible. The main aim of the research described in this thesis was to investigate the possible involvement of differentiation of GBM cells in the invasive behavior of GBM. First, we discovered that two important microenvironmental factors in GBM, namely TGF-β and hypoxia, induced a mesenchymal transdifferentiation in GBM cells thereby enhancing its invasive potential. The transcription factors ZEB1 was identified as a critical regulator of this process. Second, the involvement of the differentiation state in GBM in determining their invasive capacity was examined. Interestingly, differentiated GBM cells appeared more invasive than the undifferentiated GBM (stem) cells. Further we showed that differentiated cells could also revert back and gain many of the properties associated with stem cells hence sustaining tumorigenicity. These novel findings indicate that mesenchymal transition and differentiation enhance the invasive capacity of GBM cells. Inhibition of the identified pathways contribute to heterogeneity and provide potential therapeutic targets to reduce the infiltrating behavior of this aggressive and lethal brain tumor.

AB - Glioblastoma (GBM) is the most aggressive brain tumor and its diffuse infiltration in to the normal brain tissue is one of the main causes for poor prognosis, making complete surgical removal virtually impossible. The main aim of the research described in this thesis was to investigate the possible involvement of differentiation of GBM cells in the invasive behavior of GBM. First, we discovered that two important microenvironmental factors in GBM, namely TGF-β and hypoxia, induced a mesenchymal transdifferentiation in GBM cells thereby enhancing its invasive potential. The transcription factors ZEB1 was identified as a critical regulator of this process. Second, the involvement of the differentiation state in GBM in determining their invasive capacity was examined. Interestingly, differentiated GBM cells appeared more invasive than the undifferentiated GBM (stem) cells. Further we showed that differentiated cells could also revert back and gain many of the properties associated with stem cells hence sustaining tumorigenicity. These novel findings indicate that mesenchymal transition and differentiation enhance the invasive capacity of GBM cells. Inhibition of the identified pathways contribute to heterogeneity and provide potential therapeutic targets to reduce the infiltrating behavior of this aggressive and lethal brain tumor.

M3 - Thesis fully internal (DIV)

SN - 978-90-367-7856-5

PB - University of Groningen

CY - [Groningen]

ER -

Role of differentiation in glioblastoma invasion

Samenvatting

Toegang tot document

Handle.net

Vingerafdruk

Citeer dit