Radioresistant mouse pheochromocytoma cell lines.

Area of Science:

• Oncology
• Radiation Biology
• Genetics

Background:

• Metastatic pheochromocytoma/paraganglioma (PCC/PGL) presents limited therapeutic options.
• Peptide receptor radionuclide therapy (PRRT) can sometimes lead to metastatic eruption, suggesting radioresistant tumor cell phenotypes.
• The mechanisms of radioresistance in PCC/PGL are poorly understood, and suitable experimental models are lacking.

Purpose of the Study:

• To establish novel preclinical models of radioresistant pheochromocytoma/paraganglioma (PCC/PGL).
• To investigate the impact of hypoxia-inducible factor 2α (HIF-2α) on radioresistance development in PCC/PGL.
• To characterize DNA repair capacity and morphological changes in response to fractionated irradiation.

Main Methods:

• Two genetically modified mouse pheochromocytoma (MPC) cell lines, differing in HIF-2α expression (MPC+HIF-2α and MPC+EV), were subjected to fractionated X-ray irradiation.
• Two irradiation protocols were employed: recovery between fractions (recIR) and daily irradiation (dayIR).
• Changes in cell morphology, growth rate, and DNA repair marker (γH2AX) were assessed.

Main Results:

• MPC cell lines were conditioned to tolerate fractionated X-ray doses up to 2 Gy/day without significant growth inhibition.
• Conditioned cell lines exhibited enhanced DNA repair capacity.
• MPC+HIF-2α cells demonstrated the highest increase in radioresistance, tolerating up to 5 Gy/day.
• Daily irradiation (dayIR) induced more pronounced morphological changes (clustering, slower growth) compared to recovery irradiation (recIR).

Conclusions:

• Established X-ray-conditioned MPC cell lines serve as valuable models for studying radioresistant PCC/PGL.
• These models will facilitate further research into the mechanisms of acquired radioresistance and PRRT-induced metastasis.
• The models can be utilized to test advanced PRRT and complementary therapies for improved theranostic strategies.