Mitochondrie transfer, signalveier for invasjon og "microtube" formasjon i glioblastom
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 mitochondria are transferred between stromal cells and tumor cells through microtubes which could contribute to invasion. In the current project, we want to verify this phenomenon in vivo in animal experiments and investigate specifically the transfer of mitochondria, 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 signaling components responsible for microtube formation and mitochondria transfer. In addition, tumor cells will be implanted that have been depleted of mitochondria in vitro. In this project we want to characterize the impact of mitochondria transfer on tumor metabolism and tumor cell invasion and characterize signaling pathways that are important for this process-
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 understanding 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 performed 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.
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 mitochondria are transferred between stromal cells and tumor cells through microtubes which could contribute to invasion. In the current project, we want to verify this phenomenon in vivo in animal experiments and investigate specifically the transfer of mitochondria, 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 signaling components responsible for microtube formation and mitochondria transfer. In addition, tumor cells will be implanted that have been depleted of mitochondria in vitro. In this project we want to characterize the impact of mitochondria transfer on tumor metabolism and tumor cell invasion and characterize signaling pathways that are important for this process-
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 understanding 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 performed 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.