Forsøksdyr: Influence of TGF-beta signaling on microtube formation and invasion of human glioblastoma

Godkjenningsdato 02.01.2018

Godkjenningsperiode 02.01.2018-31.12.2020

1. forsøkets formal
Glioblastoma is the most aggressive primary brain tumor. Invasive tumor cells escape current treatment strategies and lead to tumor recurrence. It has been shown that microtubes, which are cytplasmatic extension of glioblastoma cells, are important for cell communication and invasion. In cell culture experiments, we have shown that TGF-beta signaling is important for microtube formation and migration of glioblastoma cells. In the current project, we want to verify that TGF-beta signaling is also important in vivo in animal experiments for the formation of microtubes and the invasive process. We will use human glioblastoma cell cultures for implantation into the brain of nude rats. The cells will be modified for knockdown of different components of the TGF-beta pathway. In addition we will treat the animals with a TGF-beta inhibitor that is currently used in clinical trials. We want to analyze if TGF-beta pathway is important in the invasive process and if specific components of the TGF-beta pathway can be targeted specifically, which would lead to development of novel therapeutic strategies.
2. forventede skadevirkninger på dyrene
We will implant brain tumor cells into the brain of nude rats. Tumors will develop and imaged regularly by MRI. Form our previous experiences, these treatments are well tolerated by the animals. When tumors reach a big size on MRI, animals will be euthanized, preferably before symptoms develop.
3. forventet vitenskapelig eller samfunnsmessig nytteverdi
Glioblastoma is a highly aggressive tumor of the brain with dismal prognosis. Basic uncerstanding of resistance mechanisms and development of new treatment strategies are needed to improve the survival of these patients.
4. Antall dyr og art
Nakne rotter (rnu-/rnu-); Antall: 288
5. Erstatning, reduksjon, forbedring
We have already perfomed extensive experiments in the cell culture. In order to evaluate a therapeutic potential, we need to perform in vivo experiments. In addition tumor cell invasion is highly dependent on the tumor microenvironment which is very complex and cannot be fully mimicked in vitro.