title: The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets.
abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs) are exclusively present on the biliary tract. Importantly, the GH-IGF-SST system components have been indicated as regulators of hepatocarcinogenesis. Reduction of GH binding affinity to GH receptor, decreased serum IGF1 and increased serum IGF2 production, overexpression of IGF1 receptor, loss of function of IGF2 receptor and appearance of SSTRs are frequently observed in human HCC. In particular, recently, many studies have evaluated the correlation between increased levels of IGF1 receptors and liver diseases and the oncogenic role of IGF2 and its involvement in angiogenesis, migration and, consequently, in tumour progression. SST directly or indirectly influences tumour growth and development through the inhibition of cell proliferation and secretion and induction of apoptosis, even though SST role in hepatocarcinogenesis is still opened to argument. This review addresses the present evidences suggesting a role of the GH-IGF-SST system in the development and progression of HCC, and describes the therapeutic perspectives, based on the targeting of GH-IGF-SST system, which have been hypothesised and experimented in HCC.
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Via Sergio Pansini, 5, Naples 80131, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pivonello
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Via Sergio Pansini, 5, Naples 80131, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: De Martino
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Via Sergio Pansini, 5, Naples 80131, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Negri
authors.affiliation: IRCCS Fondazione SDN, Naples, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Cuomo
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Via Sergio Pansini, 5, Naples 80131, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cariati
authors.affiliation: National Cancer Institute G Pascale Foundation, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Izzo
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Via Sergio Pansini, 5, Naples 80131, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Via Sergio Pansini, 5, Naples 80131, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
keywords: GH-IGF1 axis; Hepatocarcinogenesis; Hepatocarcinoma; Normal liver; Somatostatin; Somatostatin receptors