title: Changes in expression of transferrin, insulin-like growth factor 1, and interleukin 4 receptors after irradiation of cells of primary malignant brain tumor cell lines.
abstract: Various immunotoxins have been developed for the treatment of cancer. The toxin is internalized by target cells through cell-surface receptors, and it is essential for these receptors to be expressed for the immunotoxin to have specific anti-tumor activity. Radiation therapy is one of the main treatment modalities for primary malignant brain tumors. The purpose of this study was to determine whether radiation influences the expression of cell-surface receptors. Cells of one human medulloblastoma (Daoy) and two glioblastoma (U373-MG and T98-G) cell lines were tested by exposing the cells to a single dose of 5 Gy gamma rays. Expression of transferrin receptors, type-1 insulin-like growth factor receptors (IGF1R), and interleukin 4 receptors (IL4R) was measured by flow cytometry analysis on unirradiated cells and on cells 3 to 120 h after irradiation. In Daoy cells, the absolute expression index of transferrin receptors increased during the 24 h after irradiation with the greatest change of 26% above control at 9 h. The absolute expression index of IGF1R increased 26.5% above control at 12 h. The absolute expression index of IL4R decreased 9 h after irradiation. In U373-MG cells the absolute expression index of transferrin receptors increased during the 24 h after irradiation, and the greatest increase was 45% above control at 9 h. The absolute expression index of IGF1R increased during the 12 h after irradiation with a maximum increase of 33% above control at 6 h. The absolute expression index of IL4R decreased with time after irradiation. In T98-G cells, the absolute expression index of both transferrin receptors and IL4R decreased after irradiation. The results suggest that the expression of growth factor receptors on brain tumor cells may be influenced by radiation. The effect of ionizing radiation on receptor expression should be considered when administration of targeted toxin is combined with radiation. Similar studies with other growth factor receptors used in targeted toxin therapy are recommended.
authors.affiliation: Department of Neurosurgery, Therapeutic Radiology-Radiation Oncology, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
authors.forename: Ki-Uk
authors.initials: KU
authors.lastname: Kim
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Hsiao-Tzu
authors.initials: HT
authors.lastname: Ni
authors.forename: Kwan H
authors.initials: KH
authors.lastname: Cho
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.forename: Walter A
authors.initials: WA
authors.lastname: Hall
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D014168:Transferrin; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects
chemical_list: D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4; D011990:Receptors, Transferrin; D014168:Transferrin; D017526:Receptor, IGF Type 1