Human T-leukemia and T-lymphoma express glutamate receptor AMPA GluR3, and the neurotransmitter glutamate elevates the cancer-related matrix-metalloproteinases inducer CD147/EMMPRIN, MMP-9 secretion and engraftment of T-leukemia in vivo

Leuk Lymphoma. 2009 Jun;50(6):985-97. doi: 10.1080/10428190902878448.


Glutamate is the major excitatory neurotransmitter of the nervous system. We previously found that glutamate activates normal human T-cells, inducing their adhesion and chemotaxis, via its glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype 3 (GluR3) expressed in these cells. Here, we discovered that human T-leukemia (Jurkat) and cutaneous sezary T-lymphoma (HuT-78) cells also express high levels of GluR3. Furthermore, glutamate (10 nM) elevates CD147/EMMPRIN, a cancer-associated matrix metalloproteinases (MMPs) inducer, promoting spread of many tumors. Glutamate-induced CD147 elevation in both cancerous and normal human T-cells was mimicked by AMPA (glutamate/AMPA-receptor agonist) and blocked by CNQX (glutamate/AMPA-receptor antagonist). Importantly, glutamate also increased gelatinase MMP-9 secretion by T-lymphoma. Finally, ex vivo pre-treatment of T-leukemia with glutamate enhanced their subsequent in vivo engraftment into chick embryo liver and chorioallantoic membrane. Together, these findings reveal that glutamate elevates cancer associated proteins and activity in T-cell cancers and by doing so may facilitate their growth and spread, especially to and within the nervous system. If so, glutamate receptors in T-cell malignancies should be blocked.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Basigin / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Chick Embryo
  • Chorioallantoic Membrane / metabolism
  • Chorioallantoic Membrane / surgery
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Glutamic Acid / pharmacology*
  • Graft Survival / drug effects
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Jurkat Cells
  • Leukemia, T-Cell / genetics
  • Leukemia, T-Cell / metabolism
  • Leukemia, T-Cell / pathology
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Transplantation / methods
  • Polymerase Chain Reaction
  • Receptors, AMPA / metabolism*
  • Transplantation, Heterologous


  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 3
  • Basigin
  • Green Fluorescent Proteins
  • Glutamic Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Matrix Metalloproteinase 9