Apoptotic Events in Glioma Activate Metalloproteinases and Enhance Invasiveness

Abstract

A cancer of the brain that arises from supporting tissue (glial cells) is referred to as a glioma. Glioblastomas are fast growing gliomas and can be referred to as a Grade IV astrocytomas or glioblastoma multiformes (GBMs). GBMs that affect the brain do not readily spread to parts of the body outside of the brain, but they are highly invasive and invade surrounding tissue in the brain. The persistent invasiveness, which is extremely difficult to reverse, is what makes GBMs so deadly. Therapeutic regimens for GBM and other high grade gliomas have fallen short of providing effective treatment. Clinical studies comparing chemotherapeutic agents have indicated increased tumor shrinkage and a very slight increase in median survival times, but no evidence for an increase in survival rates [1, 2]. More recent clinical studies employing surgery with the use of chemotherapeutic regimens in combination with radiation therapy or by receptor mediated growth hormone deprivation are slightly more effective in increasing median survival times, but again have had limited success in increasing the overall survival rate in patients being treated for primary or recurrent GBM [3-7]. Clinicians and neurosurgeons are diligently pursuing new treatments and provide hope for patients and their families [8, 9]. However, the difficulties of complete resection, the resistance to radiation and other therapies and particularly the intractable malignant invasiveness still remains at the root of the very poor survival prognosis for patients with GBM and other high grade gliomas. Despite extensive studies regarding the clinical aspects of GBM very little is known about the behavior of GBM during apoptosis. The ideas pursued in this paper are relevant to apoptotic cells within a glioma enhancing the invasiveness of the apoptotic resistant cells and thus contributing to the tumor’s malignant properties.