Brain tumors and stem cells. How stem cells become brain cancer. 9
Stem cells is a very hotly discussed topic. Dr. Anton Titov, MD. That includes brain stem cells. It is less known that stem cells can give rise to brain tumors. The most aggressive brain tumors [GBM (glioblastoma multiforme) arise from brain stem cells. You have done very interesting research on stem cell biology of brain tumors. Could you please discuss the brain stem cells? How they give rise to the brain tumors? Dr. Anton Titov, MD. How that can be used in diagnosis and treatment of brain tumors? So you are correct. Dr. Sebastian Brandner, MD. Stem cells over the last 10 years have been really in the focus of the brain tumor pathogenesis. Brain stem cells are a key to the pathology and biology of brain tumors. But let’s look back through history. 50 or 80 years back, first in 1930s and 1940s, first ideas about brain stem cells appeared. The first mouse models have predicted that there might be a type of cell in the brain. Stem cells were known for nearly 100 years. Stem cells were postulated for nearly 100 years. Since 1930s and 40s, there were very primitive-appearing research methods. It was chemical carcinogenesis. These brain tumors always arose from areas that are close to brain stem cell regions. In the 1960s and 70s additional clinical trials were done and they showed brain stem cells. I went to review these old papers just a couple of years ago. I put it all information about brain stem cells together in a review article. Dr. Sebastian Brandner, MD. I realized that many brain tumors were located in regions which are stem cell-rich. I understood this fact by looking at old photographs from the 1960s. Brain tumor stem cell concept evolved further in the 1990s. A certain type of mouse models were generated. You can specifically inactivate and silence genes that are known to be involved in a brain tumors pathogenesis. This was p53 tumor suppressor gene. Also there were other genes. Retinoblastoma gene, RB gene. It was also the retinoblastoma gene and p10 gene. So all these genes have been tagged with little tags. Sometimes you then put a little enzyme into the brain. These tags are pulled together and the gene between them is deleted. That is called “conditional knockout mouse models”. Dr. Sebastian Brandner, MD. We have been using those to demonstrate that stem and progenitor cells in the adult mouse brain can give rise to proper brain tumors. We have modeled astrocytomas. We have modeled primitive neural tumors. We have modeled oligodendrogliomas. We can show that sometimes we introduce into the stem cell layer in the mature brain. We put stem cells into adult brain. These mutations give rise to gliomas. Dr. Anton Titov, MD. Brain tumors appear selectively in this cell population. We are not the only ones doing research on brain tumor stem cells. There are many other groups who have done that with different methodologies. So this is a very strong parallel evidence. It points all to the same role of brain stem cells in brain tumors. If something goes wrong with the growth signals of a stem cell, then they can start growing autonomously. Brain tumor stem cells grow without being controlled. They grow without being inhibited by the inhibiting factors. Dr. Anton Titov, MD. So brain tumor stem cells are just out of control. They keep growing. First, it is a small little growth. Dr. Sebastian Brandner, MD. Then brain tumor stem cells start infiltrating the brain. They form a proper brain tumor. Stem cells promise many treatments. But it is stem cells that give rise to brain tumors. This includes gliomas and glioblastoma multiforme (GBM). Glioblastoma is the most aggressive intrinsic brain tumor. Leading expert in brain tumor diagnosis explains the link between stem cells and brain tumors.
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