Monday, August 4, 2014

The Origin Of Glioblastoma Multiforme

By Annabelle Holman


Primary brain tumors, those that originate in the brain, are more frequent in children and older adults. One feature that sets brain tumors apart from those arising from other tissues in the body is their inability to exit the brain to form secondary, or metastatic, tumors in other organs. They do, however, have a tendency to invade the surrounding brain to establish new tumors within the cranium. The most serious type of intrinsic brain tumor is called glioblastoma multiforme, or GBM.

Brain tumors are the second most common cause of cancer deaths in males and females under the age of 20. After leukemia, intrinsic brain tumors are the second leading cause of cancer deaths in men between the ages of 20 and 29. They are the fifth most frequent cause of cancer deaths among females between the ages of 20 and 39.

Luckily, GBM is infrequent; there are no more than two or three new cases per 100,000 individuals and account for only 20% of all intracranial neoplasms. Their propensity to invade the surrounding brain tissue means that it is not possible for them to be completely eradicated by surgical means. Try scraping off every bit of butter from a slice of toast.

The type of cell that gives rise to GBM is the glial cell, of which there are three types. Nerve cells lose their ability to divide once they have reached terminal differentiation. Glial cells, on the other hand, are able to divide throughout the life of the individual. Evidence from both in vivo studies in the '60s and in vitro studies in the '90s and early 21st century support the hypothesis that most, if not all, intrinsic brain tumors begin forming in the developing fetus.

Glial cells come in three different forms: microglia, astrocytes and oligodendrocytes. Of these, astrocytes and astrocytic tumors, are the most common. The nastiest, most malignant and most deadly variant of astrocytoma is the GBM, which has a median time of survival without treatment of less than five months.

Astrocytes are characterized by their starry morphology and the presence of glial fibrillary acidic protein (GFAP). The normal function of astrocytes is to supply nutrients to nerve cells, support the vascular cells that comprise the blood brain barrier and repair damaged cells following trauma. New studies suggest that they communicate with neuronal cells by secreting glutamate, the brain's main excitatory neurotransmitter.

Oligodendrocytes have fewer spiny processes than astrocytes. Their main function is to produce the myelin sheath that surrounds nerve cell axons to insulate them and speed up nerve impulse transmission. A single oligodendrocyte can service as many as 50 different nerve cells. It is the myelin sheath that is attacked by the immune system in the autoimmune condition known as multiple sclerosis (MS).

Microglia are the macrophages of the central nervous system. These cells act quickly recognize and destroy foreign bodies, engulf them and present them to other cells of the immune system, called T-cells, before they get the chance to interfere with healthy brain tissue. Microglia exist in two different forms. Resting cells, which resemble tiny astrocytes, and activated microglia, which are more bloated in appearance.




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