Mechanisms of Invasion in Glioblastoma: Extracellular Matrix, Ca2+ Signaling, and Glutamate

Abstract

Glioblastoma (GBM) is the most common and malignant form of primary brain tumor with a median survival time of 14–16 months in GBM patients. Surgical treatment with chemotherapy and radiotherapy may help increase survival by removing GBM from the brain. However, complete surgical resection to eliminate GBM is almost impossible due to its high invasiveness. When GBM cells migrate to the brain, they interact with various cells, including astrocytes, neurons, endothelial cells, and the extracellular matrix (ECM). They can also make their cell body shrink to infiltrate into narrow spaces in the brain; thereby, they can invade regions of the brain and escape from surgery. Brain tumor cells create an appropriate microenvironment for migration and invasion by modifying and degrading the ECM. During those processes, the Ca2+ signaling pathway and other signaling cascades mediated by various ion channels contribute mainly to gene expression, motility, and invasion of GBM cells. Furthermore, GBM cells release glutamate, affecting migration via activation of ionotropic glutamate receptors in an autocrine manner. This review focuses on the cellular mechanisms of glioblastoma invasion and motility related to ECM, Ca2+ signaling, and glutamate. Finally, we discuss possible therapeutic interventions to inhibit invasion by GBM cells.

Gene Expression Analysis of Glioma Neural Stem Cells Shows Disturbed Amino Acids Metabolism and Axonal Growth Cone Dynamics in Glioblastoma Multiforme

“…Axonal growth cone is responsible for determination of cell growth direction, extracellular motility(ECM), and provides growth direction of the axon in that direction(40). Studies have shown that disturbed ECM processes lead to invasion and motility in GBM(41). Since glial cells and axons in GBM lead to aggressive growth which ultimately to lethal tumor formation, could state lack of growth directions from axonal growth cone processes due to the down-regulation of this particular process in GBM.…”

“…Axonal growth cone is responsible for determination of cell growth direction, extracellular motility(ECM), and provides growth direction of the axon in that direction (40). Studies have shown that disturbed ECM processes lead to invasion and motility in GBM (41).Since glial cells and axons in GBM lead to aggressive growth which ultimately to lethal tumor formation, could state lack of growth directions from axonal growth cone processes due to the down-regulation of this particular process in GBM. However investigation of the axonal growth cone pathway in association of GBM could help us gain more insights in progression of this horrendous disease.In association with this, drawing a conclusion to association of beta-amyloid protein binding pathways and it's down-regulation in GBM, here reveal new insights in progression of GBM.…”

Non-Coding RNAs and Brain Tumors: Insights Into Their Roles in Apoptosis

“…Despite much research and clinical investigation in recent years, the prognosis and treatment of glioma are not so desirable ( Xu et al, 2020 ). Great proliferation rate with high resistance to therapies, sensitivity of the CNS and low ability to repair itself, and inability of most drugs to pass the blood brain barrier (BBB) prevent impressive treatment of glioma ( So et al, 2021 ). One of the malignant glioma’s hallmarks is its ability to infiltrate the brain, leads to avoidable recurrence post local therapy ( So et al, 2021 ).…”

“…Great proliferation rate with high resistance to therapies, sensitivity of the CNS and low ability to repair itself, and inability of most drugs to pass the blood brain barrier (BBB) prevent impressive treatment of glioma ( So et al, 2021 ). One of the malignant glioma’s hallmarks is its ability to infiltrate the brain, leads to avoidable recurrence post local therapy ( So et al, 2021 ). Nowadays, existing therapeutic approaches include resection surgery, chemotherapy, radiotherapy, and combination therapies.…”

Identification of potential targets of the curcumin analog CCA-1.1 for glioblastoma treatment : integrated computational analysis and in vitro study

“…Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors 1 . GBM arises from astrocytes that support nerve cells and invade nearby brain cells 2 . It can affect children; however, it is more common in adults aged 40–75 years 3 .…”