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Strain-specific metastatic phenotypes in pheochromocytoma allograft mice

Martin Ullrich1, Josephine Liers1,2, Mirko Peitzsch3

  • 1Department of Radiopharmaceutical and Chemical Biology, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.

Endocrine-Related Cancer
|October 6, 2018
PubMed

Insights

Developing reliable preclinical models for metastatic pheochromocytoma and paraganglioma is crucial. This study identified SCID/beige and SKH1 mice as effective models for studying metastatic disease and theranostic approaches.

Area of Science:

  • Oncology
  • Endocrinology
  • Preclinical Research

Background:

  • Metastatic pheochromocytomas and paragangliomas are challenging to treat.
  • Somatostatin receptor-targeted endoradiotherapy shows promise but requires effective preclinical models.
  • Combination radiosensitization therapy may enhance treatment efficacy.

Purpose of the Study:

  • To characterize metastatic spread of mouse pheochromocytoma (MPC) cells in different immunologic mouse models.
  • To establish reliable in vivo models for studying metastatic pheochromocytoma and paraganglioma.
  • To evaluate the suitability of these models for theranostic approaches.

Main Methods:

  • Luciferase-expressing MPC cells were injected intravenously into various mouse strains (NMRI-nude, SCID/SHO, SCID/beige, SKH1).
  • Bioluminescence imaging was used to monitor metastatic spread.
  • Urine samples were analyzed using liquid chromatography tandem mass spectrometry for catecholamine metabolites.
  • Positron emission tomography and immunohistochemistry assessed somatostatin receptor expression.

Main Results:

  • Intravenous injection led to suboptimal metastasis in NMRI-nude and SCID/SHO mice.
  • Depletion of natural killer (NK) cells enhanced metastasis in NMRI-nude mice.
  • Reproducible metastatic spread was observed in SCID/beige and SKH1 mice.
  • All metastases maintained somatostatin receptor expression.
  • Comparable renal monoamine excretion profiles were observed in subcutaneous and metastatic models.

Conclusions:

  • SCID/beige and SKH1 mice provide reproducible, clinically relevant models for metastatic pheochromocytoma and paraganglioma.
  • These models enable precise monitoring of disease progression.
  • The models facilitate further research into theranostic strategies for these tumors.

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