Hepatic Neuroendocrine Tumor Metastasis Proliferation is Hepatocyte Regulated Via a 5HT7 Mediated Induction of an IGF 1 and HGF Feedback Loop Mediated by cAMP, PKA-independent pAKT and pCREB

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Introduction: Carcinoid serotonin (5-HT) causes local fibrosis but the effect of 5-HT on hepatocytes has not been established. We hypothesized that tumors and hepatocytes form a metastasis-supportive environment.

Aim(s): To examine effects of 5-HT on proliferation, signaling pathways and growth factor transcription and secretion in isolated pure hepatocyte preparations.

Materials and methods: 1) Hepatocyte 5-HT receptor profile by PCR and DNA sequencing, 2) Delineation of the proliferative effects of 5-HT on hepatocytes (WST-1 uptake), 3) Examine 5-HT-mediated signaling pathways (PKA, cAMP, pCREB, AKT, ERK - ELISA and western blot) and 4) Effect of 5-HT on growth factor (IGF-I/HGF) synthesis and secretion (ELISA).

Conference: 8th Annual ENETSConcerence (2011)

Presenting Author:

Authors: Svejda B, Kidd M, Lawrence B, Alaimo D, Schimmack S,

Keywords: 5-HT, carcinoid, growth factor, HGF, IGF-I, hepatocyte, liver, proliferation, neuroendocrine tumor,