The somatostatin system – A silent messenger in pheochromocytomas and paragangliomas?

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Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine neoplasms (NENs) arising from neural crest-derived chromaffin cells. Due to the abundance of somatostatin receptors (SSTs) on the surface of most NENs, somatostatin analogues (SSAs) have become a cornerstone in their diagnosis and treatment. However, while PPGLs exhibit this feature, their functional responsiveness to SSAs remains limited, with the underlying cause of this resistance being still elusive.

Aim(s): We aim to elucidate the signaling elements of the somatostatin system that, through their disturbance in PPGLs, are responsible for the poor response of these tumors to medical therapy with SSAs.

Materials and methods: The expression pattern of the different SSTs was analysed in three cohorts of RNA-seq data. Subsequently, in vitro assays were performed on available human (SK-N-AS, including wildtype and SDHB knockdown models) and rat (PC-12) cell line models. Experiments were aimed to assess the response to treatment with classical SSAs and SST-selective agonists both on functional readouts (proliferation, apoptosis, migration, colony formation) and signaling mechanisms (phosphoarray of key signaling pathways, cAMP levels).

Conference:

Presenting Author:

Authors: García Vioque V, Moreno-Montilla M, Blázquez-Encinas R, Barlier A, Arroba E,

Keywords: pheochromocytomas, paragangliomas, neuroendocrine tumor, somatostatin analogues, treatment resistance,