The migration of
tumor cells is a prerequisite for
tumor cell invasion and
metastasis development, which accounts for over 90% of
cancer mortality. Therefore a major focus of current
tumor biological research is the study of those factors that regulate
tumor cell migration. Those
chemokines and
neurotransmitters that bind to
G-protein coupled receptors (also known as
serpentine receptors) are the most prominent of these factors.
Neurotransmitters have been identified that have not only a stimulatory (e.g.
norepinephrine) effect, but an inhibitory effect (e.g.
GABA) as well. This is an especially fortuitous development, because many known agonists and antagonists of
neurotransmitter receptors are currently being successfully used in the treatment of other pathological conditions (e.g. beta-blockers in the treatment of
cardiovascular diseases). Likewise,
chemokine receptor antagonists, which are under development for the treatment of HIV or
rheumatoid arthritis, may be effective tools for the inhibition of
chemokine-driven
tumor cell migration as well. A further approach to inhibit
tumor cell migration arises from the investigation of the relevant signal transduction pathways. The PKC alpha, for example, is a key
enzyme in the regulation of
tumor cell migration, but not of leukocyte migration. It thus offers a selective target opportunity for specific pharmacological agents to interfere with
tumor cell migration. In this review we therefore summarize the current findings on those
serpentine receptors involved in the
neurotransmitter- and
chemokine-regulated
tumor cell migration, on the underlying signal transduction pathways, and on the opportunities to inhibit
tumor cell migration and ultimately
metastasis development with
pharmaceutical agents.