TY - JOUR
T1 - Altered glutamatergic and inflammatory pathways promote glioblastoma growth, invasion, and seizures
T2 - An overview
AU - Feyissa, Anteneh M.
AU - Rosenfeld, Steven S.
AU - Quiñones-Hinojosa, Alfredo
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/12/15
Y1 - 2022/12/15
N2 - Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain cancer. Drug-resistant seizures and cognitive impairments often accompany the invasion of the neocortex by the GBM cells. Recent studies suggest that seizures and glioma share common pathogenic mechanisms and may influence each other. One explanation for the close link between the two conditions is elevated glutamate in the tumor microenvironment (TME) due to an increased expression of the cystine-glutamate transporter with ensuing overactivity of glutamatergic signaling. Excess glutamate in the TME also encourages the polarization of pro-inflammatory tumor-associated macrophages to an anti-inflammatory state causing TME immunosuppression and facilitating tumor invasion. Besides, the recently discovered glutamatergic neurogliomal synapses, partially via their influence on calcium communication in microtube-connected tumor cell networks, drive the progression of GBM by stimulating glioma invasion and growth. Moreover, neuroinflammatory pathways have been shown to have several points of intersection with glutamatergic signaling in the TME, further promoting both epileptogenesis and oncogenesis. Future studies identifying pharmacotherapeutics targeting these elements is an extremely attractive therapeutic strategy for GBM, for which very little therapeutic progress has been made in the past two decades.
AB - Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain cancer. Drug-resistant seizures and cognitive impairments often accompany the invasion of the neocortex by the GBM cells. Recent studies suggest that seizures and glioma share common pathogenic mechanisms and may influence each other. One explanation for the close link between the two conditions is elevated glutamate in the tumor microenvironment (TME) due to an increased expression of the cystine-glutamate transporter with ensuing overactivity of glutamatergic signaling. Excess glutamate in the TME also encourages the polarization of pro-inflammatory tumor-associated macrophages to an anti-inflammatory state causing TME immunosuppression and facilitating tumor invasion. Besides, the recently discovered glutamatergic neurogliomal synapses, partially via their influence on calcium communication in microtube-connected tumor cell networks, drive the progression of GBM by stimulating glioma invasion and growth. Moreover, neuroinflammatory pathways have been shown to have several points of intersection with glutamatergic signaling in the TME, further promoting both epileptogenesis and oncogenesis. Future studies identifying pharmacotherapeutics targeting these elements is an extremely attractive therapeutic strategy for GBM, for which very little therapeutic progress has been made in the past two decades.
KW - Brain-tumor
KW - Glioblastoma
KW - Glioma-neuron synapse
KW - Glioma-related seizures
KW - Glutamatergic pathway
KW - Inflammation
KW - Seizures
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UR - http://www.scopus.com/inward/citedby.url?scp=85141500757&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2022.120488
DO - 10.1016/j.jns.2022.120488
M3 - Article
C2 - 36368135
AN - SCOPUS:85141500757
SN - 0022-510X
VL - 443
JO - Journal of the neurological sciences
JF - Journal of the neurological sciences
M1 - 120488
ER -