Studies on the role of dopamine and serotonin in tumors and their microenvironment
|PhD ceremony:||M.A.M. Peters, MSc|
|When:||October 26, 2020|
|Supervisor:||prof. dr. I.P. (Ido) Kema|
|Co-supervisors:||dr. S.F. Oosting, dr. A.M.E. (Annemiek) Walenkamp, dr. J. Meijer|
|Where:||Academy building RUG|
|Faculty:||Medical Sciences / UMCG|
Platelet activation in aberrant tumor blood vessels results in release of platelet content in the tumor microenvironment. The neurotransmitters and hormones dopamine and serotonin are stored in the dense granules of platelets. Preclinical studies showed that they can influence tumor behavior.
The aim of the research described in this thesis is to increase insight into the role of dopamine and serotonin in cancer. The effect of dopamine and the dopamine receptor D2 agonist quinpirole on tumor microvessel density and tumor growth was studied in an in ovo ovarian cancer model. Quinpirole reduced tumor growth and microvessel density, but dopamine did not. In order to evaluate which tumor types express dopamine and serotonin receptors, we screened a broad range of solid tumors using functional genomic mRNA profiling and immunohistochemistry. We found overexpression of serotonin receptor 2B in many tumor types. To understand how circulating serotonin could be involved, we measured concentrations of serotonin as well as its precursors and metabolites in plasma and platelets of various patient groups. We found low platelet serotonin concentrations in patients with metastatic renal cell carcinoma and metastatic pancreatic neuroendocrine tumors. We also observed extremely low plasma and platelet serotonin concentrations in users of serotonin reuptake inhibitors. Finally, in contrast to previous reports, we demonstrated with a new sensitive method that platelets do not contain melatonin, which is a metabolite of serotonin.