Université de Strasbourg

USIAS Fellows seminar: Cell secretion deregulation in neuroendocrine tumors

Le 21 février 2018
De 12h30 à 14h00
Salle Amériques, MISHA, University of Strasbourg

By Stéphane Gasman, USIAS Fellow 2015

Cancer is the second leading cause of death after heart disease. Neuroendocrine tumors (NETs) constitute a large family of neoplasms arising from hormone/peptide-secreting cells, cells that release hormones into the blood in response to a signal from the nervous system. NETs (both benign and malignant) often lead to deregulation such as higher-than-normal amounts of hormones. This can cause many different symptoms which can become serious problems in themselves. 

The incidence of NETs has increased considerably during the last 30 years and NETs are underserved by targeted therapies other than surgery, which limits the possible interventions and reduces patient survival rates.

Our USIAS funding allowed us to test an interesting line of thought never proposed so far: to consider tumor cell secretion as a potential target. Indeed, although NETs are heterogeneous, a common critical feature is the dysfunction of their secretory activity leading to hypersecretion. Such uncontrolled secretion cause serious illness and complications and could be directly related to the aggressiveness of the tumor. For example, our main experimental model, a NET arising from the chromaffin cells of the adrenal medulla named pheochromocytoma, is characterized by an excess of catecholamine secretion leading to hypertension, cardiomyopathy and high risk of stroke. Although this aspect is well known by clinicians, it has never been explored at the cellular and mole­cular level. 

During this project, we have analyzed the mechanisms leading to this aberrant se­cre­tion of catecholamine through the highly sensitive carbon fiber amperometry technique combined with quantitative proteomic analysis on human tumors. Uncovering why and how secretion in neuroendocrine tumors becomes uncontrolled will help to develop therapeutic strategies aiming to prevent hyper-secretion of the tumor, hence decreasing the associated-clinical risks as well as the tumor growth itself.   

 

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