Novel therapeutic strategies for the treatment of pheochromocytoma

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 37-82-Pheochromocytoma & Paraganglioma
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-60
Christian G Ziegler*1, Martin Ullrich2, Andrew V Schally3, Ralf Bergmann4, Jens Pietzsch5, Monika Ehrhart-Bornstein6, Graeme Eisenhofer7 and Stefan Richard Bornstein7
1Technical Univ Dresden, Dresden, Germany, 2Techincal University of Dresden, Dresden, Germany, 3University of Miami Miller School of Medicine, Miami, FL, USA, Miami, FL, 4Helmholtz-Zenter Dresden-Rossendorf, Dresden, 5Helmholtz-Zenter Dresden-Rossendorf, Dresden, Germany, 6University Clinic Dresden, Dresden, Germany, 7University Hospital Carl Gustav Carus, Dresden, Germany

Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine producing chromaffin cells. Available treatment strategies are limited and, if the tumor has metastasized, not very effective. Interestingly, peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by highly effective anti-tumor peptide analogs. Therefore, our present study focuses on the preclinical evaluation of potential therapies for the treatment of pheochromocytoma targeting peptide hormone receptors.

Design and method

Our in vitro evaluation of peptide hormone receptor expression on a mouse pheochromocytoma (MPC) cell line and a more malignant mouse tumor tissue-derived (MTT) cell line was based on RT-PCR and immunohistological analysis. Based on these data, we evaluated the effects of cytotoxic peptide hormone analogs on cell viability, apoptosis and necrosis on MPC and MTT cells. For in vivo studies, we furthermore established a subcutaneous mouse model of PHEO based on MPCs and multimodal tumor imaging using PET, MRI, and CT as well as fluorescence and bioluminescence imaging.


Results and conclusions

Our data reveal 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 by the 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 MPCs. Similar anti-tumor effects were evidenced for AN-152 and MIA-602 also on the more aggressive MTT cells. Furthermore, using our newly established mouse model we were able to visualize the growth of MPC cell-derived subcutaneous pheochromocytomas in vivo by multimodal molecular imaging including SSTR2 PET. Additionally, ex vivo tumor characterization demonstrated unaltered peptide hormone receptor expression during in vivo tumor growth in mice.

Altogether, our current investigation provides further evidence for the usefulness of targeted peptide hormone receptor therapy as a potential new option for future treatment of malignant pheochromocytoma.

Nothing to Disclose: CGZ, MU, AVS, RB, JP, ME, GE, SRB

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