A human neuron injury model for molecular studies of axonal regeneration.

The enhancement of regeneration of damaged axons in both the peripheral and central nervous systems is a widely pursued goal in clinical medicine. Although some of the molecular mechanisms involved in the intrinsic neurite regeneration program have been elucidated, much additional study is required for development of new therapeutics. The majority of studies in the field of axonal regeneration have utilized animal models due to obvious limitations of the accessibility of human neural tissues.

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.

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.