The neurotransmitter gamma-aminobutyric acid is an inhibitory regulator for the migration of SW 480 colon carcinoma cells.
Gamma-aminobutyric acid (GABA) is the inhibitory neurotransmitter in the brain, also playing a role in diseases like epilepsy. We now show that this inhibitory neurotransmitter can also reduce migratory activity in SW 480 colon carcinoma cells. GABA reduced the norepinephrine-induced migratory activity of these cells within a three-dimensional collagen matrix to spontaneous migration levels, as was analyzed by time-lapse videomicroscopy. This inhibitory effect of GABA was mediated by the serpentine receptor GABA(B) and was intracellularly transduced by a decrease of the cyclic AMP concentration. Cancer cell migration is thus regulated by neurobiological signals, opening new possibilities for pharmacological agonists in cancer therapy.
Joseph
Jan
J
Institute for Immunology, Witten/Herdecke University, 58448 Witten, Germany.
Niggemann
Bernd
B
Zaenker
Kurt S
KS
Entschladen
Frank
F
D003994:Bucladesine / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D003994:Bucladesine; D000242:Cyclic AMP; D009638:Norepinephrine