Differences in radiosensitivity between three HER2 overexpressing cell lines.
OBJECTIVE
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.


CONCLUSIONS
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.
Steffen
Ann-Charlott
AC
Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
Göstring
Lovisa
L
Tolmachev
Vladimir
V
Palm
Stig
S
Stenerlöw
Bo
B
Carlsson
Jörgen
J
D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D011829:Radiation Dosage; D011836:Radiation Tolerance; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases