Downregulation of solute carriers of glutamate in gliosomes and synaptosomes may explain local brain metastasis in anaplastic glioblastoma.
Advanced grades of glioblastoma are highly aggressive, especially in terms of multisite spread within the brain or even to distant sites at the spinal cord. In advanced grades of glioblastoma, glutamate and glutamine are reported to be increased in concentration in the extracellular fluid. It has been reported that glutamate acts as an extracellular signaling molecule for facilitating local spread of advanced grades of glioblastoma. In the present study, we aimed to examine whether glutamate uptake mechanisms is impaired in advanced glioblastoma. The possible downregulated mechanisms of glutamate uptake would facilitate persistence of glutamate in the extracellular environment, rather than intracellular uptake. We obtained biobanked human specimens of glioblastoma and tested expression of proteins belonging to the solute carrier families of proteins that are known to function as membrane-located excitatory amino acid like glutamate transporters. The present study provides preliminary evidence of the downregulation of membrane expression of excitatory amino acid transporters solute carrier family 1 member 3 (SLC1A3) and its palmitoylated form in gliosomes, as well as SLC1A2 in the glio-synaptosomes. Compounds like riluzole used in the treatment of amyotrophic lateral sclerosis and the antibiotic ceftriaxone have the potential to facilitate glutamate uptake. These medications may be examined as adjunct chemotherapy in the massively aggressive tumor glioblastoma multiforme.
Department of Neurosurgery, Chinese PLA General Hospital, Beijing, 100853, China.
Huaiyu
H
Tong
Department of Neurosurgery, Chinese PLA General Hospital, Beijing, 100853, China.
Xinguang
X
Yu
Department of Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
Xuechun
X
Lu
Department of Neurosurgery, Chinese PLA General Hospital, Beijing, 100853, China.
Peng
P
Wang
D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015536:Down-Regulation; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D054878:Lipoylation; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013574:Synaptosomes / Q000378:metabolism* / Q000473:pathology
D027341:Excitatory Amino Acid Transporter 1; D005971:Glutamates; C493394:SLC1A3 protein, human
anaplastic glioblastoma; chemotaxis; extracellular signaling in cancer; metastasis; oncosignaling; solute carrier proteins