Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Objective
Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine producing chromaffin cells of the adrenal medulla. Especially for malignant pheochromoytoma the available treatment strategies are not very effective. Peptide hormone receptors are abundantly expressed on endocrine tumor cells and can be specifically targeted by highly effective anti-tumor peptide analogs. Our actual study focuses on the preclinical evaluation of potential peptide hormone receptor therapies for the treatment of pheochromocytoma.

Design and method
In our in vitro studies we evaluated peptide hormone receptor expression on a neuroendocrine tumors relevant mouse pheochromocytoma (MPC) cell line and a thereof established more malignant mouse tumor tissue-derived (MTT) cell line based on RT-PCR and immunohistological analysis. We also measured the effects of cytotoxic peptide hormone analogs on cell viability, apoptosis and necrosis on MPC and MTT cells. Furthermore, for our in vivo studies we established a subcutaneous mouse model of PHEO for optimization of multimodal tumor imaging using PET, MRI, and CT, fluorescence and bioluminescence imaging.

Results and conclusions
We could demonstrate significant anti-tumor effects mediated by the cytotoxic peptide hormone analogs AN-162 and AN-238 targeting somatostatin receptor 2 (sst2), by the antagonist Cetrorelix and cytotoxic analog AN-152 targeting luteinizing hormone-releasing hormone receptor (LHRH-R) as well as by the antagonist MIA-602 targeting growth hormone-releasing hormone receptors (GHRH-R) on MPC cells. Furthermore, similar anti-tumor effects were evidenced also for AN-152 and MIA-602 on more aggressive MTT cells. In our mouse model we were able to visualize tumor growth of MPC cell-derived subcutaneous pheochromocytomas in vivo by fluorescence imaging. Ex vivo tumor characterization demonstrated that peptide hormone receptors are still expressed during tumor growth in mice.
Our current investigation provides strong evidence for the usefulness of targeted peptide hormone receptor therapy for a possible future treatment of malignant pheochromocytoma.