Related Experiment Video
Updated: Jul 8, 2026
Determining Optimal Cytotoxic Activity of Human Her2neu Specific CD8 T cells by Comparing the Cr51 Release Assay to the xCELLigence System
Published on: August 8, 2012
Differences in radiosensitivity between three HER2 overexpressing cell lines
Ann-Charlott Steffen1, Lovisa Göstring, Vladimir Tolmachev
1Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
Purpose:
HER2 is a potential target for radionuclide therapy, especially when HER2 overexpressing breast cancer cells are resistant to Herceptin(R) treatment. Therefore, it is of interest to analyse whether HER2 overexpressing tumour cells have different inherent radiosensitivity.
Methods:
The radiosensitivity of three often used HER2 overexpressing cell lines, SKOV-3, SKBR-3 and BT-474, was analysed. The cells were exposed to conventional photon irradiation, low linear energy transfer (LET), to characterise their inherent radiosensitivity. The analysis was made with clonogenic survival and growth extrapolation assays. The cells were also exposed to alpha particles, high LET, from (211)At decays using the HER2-binding affibody molecule (211)At-(Z(HER2:4))(2) as targeting agent. Assays for studies of internalisation of the affibody molecule were applied.
Results:
SKOV-3 cells were most radioresistant, SKBR-3 cells were intermediate and BT-474 cells were most sensitive as measured with the clonogenic and growth extrapolation assays after photon irradiation. The HER2 dependent cellular uptake of (211)At was qualitatively similar for all three cell lines. However, the sensitivity to the alpha particles from (211)At differed; SKOV-3 was most resistant, SKBR-3 intermediate and BT-474 most sensitive. These differences were unexpected because it is assumed that all types of cells should have similar sensitivity to high-LET radiation. The sensitivity to alpha particle exposure correlated with internalisation of the affibody molecule and with size of the cell nucleus.
Conclusion:
There can be differences in radiosensitivity, which, if they also exist between patient breast cancer cells, are important to consider for both conventional radiotherapy and for HER2-targeted radionuclide therapy.
Insights
HER2-overexpressing breast cancer cells show varying inherent radiosensitivity to both conventional and alpha-particle radiation. This radiosensitivity difference is linked to affibody molecule internalization and cell nucleus size, impacting targeted radionuclide therapy effectiveness.
Area of Science:
- Oncology
- Radiation Biology
- Molecular Imaging
Background:
- Human Epidermal growth factor Receptor 2 (HER2) is a key target in breast cancer therapy.
- Resistance to Herceptin(R) highlights the need for alternative therapeutic strategies, such as radionuclide therapy.
- Understanding inherent tumor cell radiosensitivity is crucial for optimizing treatment outcomes.
Purpose of the Study:
- To investigate the inherent radiosensitivity of HER2-overexpressing breast cancer cell lines.
- To compare the response of these cell lines to low and high Linear Energy Transfer (LET) radiation.
- To explore the correlation between radiosensitivity, HER2-targeted radionuclide uptake, and cellular characteristics.
Main Methods:
- Utilized three HER2-overexpressing cell lines: SKOV-3, SKBR-3, and BT-474.
- Assessed radiosensitivity using clonogenic survival and growth extrapolation assays after photon (low LET) irradiation.
- Evaluated response to alpha particles (high LET) from (211)At decays, delivered via a HER2-binding affibody molecule ((211)At-(Z(HER2:4))(2)).
- Studied affibody molecule internalization using specific assays.
Main Results:
- Significant differences in radiosensitivity were observed among cell lines following photon irradiation, with SKOV-3 being most radioresistant and BT-474 most sensitive.
- While HER2-dependent uptake of (211)At was similar across cell lines, sensitivity to alpha particle radiation varied.
- SKOV-3 cells demonstrated the highest resistance, and BT-474 the highest sensitivity to alpha particles, correlating with affibody internalization and nuclear size.
Conclusions:
- HER2-overexpressing breast cancer cells exhibit differential inherent radiosensitivity.
- This variability in radiosensitivity, particularly to high-LET radiation, is influenced by affibody molecule internalization and cell nucleus size.
- Findings have significant implications for both conventional radiotherapy and the development of HER2-targeted radionuclide therapies.
