Primary study:

https://www.mdpi.com/1422-0067/24/3/2540

Description of results

• N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel typically researched and found in the central nervous system and in neurons

  • NMDA is used for learning, memory, information storage

• However, research in the past decades challenges this and found NMDA receptors in somatic cells too.

  • Found in research on cell competition: It is an evolutionary conserved quality control process which avoids the accumulation of viable, but not optimal, cells during development and aging

  • Glutamate, the neurotransmitter used by receptors, can activate several signaling pathways that are important for cell proliferation, differentiation, and survival.

• Researchers have found NMDA receptors in cancer cells

  • Glutamine heavily contributes to maintaining amino acids for the cancerous cell

  • The release of glutamate can be a signal for cells to activate NMDAR in cancer, driving invasive growth

  • The NMDA receptor has been found in several types of cancer and cancer cell lines, including prostate cancer, gastric cancer, breast cancer, laryngeal cancer, lung cancer, pancreatic cancer, and glioblastomas

  • The genetic knock- down of NMDAR2B reduced cell proliferation in malignant breast cancer cell–neuron co-culture (Study)

  • In addition to their antiproliferative activity, it was also demonstrated that NMDAR antagonists alter the morphology and decrease the motility of cancer cells.

    • MK-801 induced changes in the morphology of melanoma cells that resemble that of normal melanocytes and decreased cell motility (Study)

  • NMDAR and the resultant calcium signaling pathways in the tumor cells were activated by the synaptic release of glutamate, which promoted the colonization and growth of the metastatic tumor in the brain (Study)

How it compares to previous work

The study confirms many previous hunches on role of bioelectricity with cancer. We’ve confirmed that:

• Receptors typically found in neurons are found in somatic cells as well

• When using genes to knock down the expression of NMDR receptors, the cells changed in morphology to resemble normal cells

• Calcium signaling pathways, which alter the membrane potential of cells, were activated by glutamate, which then led to tumor growth

  • glutamate → active calcium signaling pathways → altering of membrane potential → tumor growth

Main strategies used to obtain results

This was an analysis of previous work. Most studies were conducted in vitro (in cell cultures) and further studies are needed to determine the potential effectiveness of NMDA receptor antagonists as cancer therapies in vivo (in animal models and humans).