Neurotensin and growth of normal and neoplastic tissues

Neurotensin (NT) is a brain-gut tridecapeptide that functions as a neurotransmitter/neuromodulator in the central nervous system (CNS) and as an endocrine agent in the periphery. NT has numerous physiologic effects on multiple organs. This review will focus on the effects of NT as a trophic factor for normal and neoplastic tissues. In this regard, NT may act as an endocrine agent or, in some instances, in a paracrine and/or autocrine fashion. These effects appear to be mediated predominantly through the G protein-coupled high-affinity NT receptor. However, some of the trophic effects may also be through the other two receptor subtypes, particularly the NT receptor type 3, which belongs to a recently identified family of sorting receptors. The signaling pathways mediating the effects of NT are multiple but most appear to activate the ERK signaling pathway, which then activates downstream transcription factors, ultimately leading to proliferation. NT may be a useful agent to enhance the growth of normal tissues such as the small bowel mucosa during periods of gut disuse or disease and, finally, the selective targeting of NT receptor subtypes on certain cancers may offer a novel strategy in the armamentarium of cancer chemotherapeutics.