Influence of tumor cell and stroma sensitivity on tumor response to radiation.
In this study, we evaluated the role of tumor cell and tumor stroma sensitivity as determinants of radiation-induced tumor growth delay. A DNA double-strand break repair-defective DNA-PKcs(-/-) tumor cell line and its radioresistant DNA-PKcs(+/+)-transfected counterpart were used to initiate tumors in nude and hypersensitive severe combined immunodeficient (SCID) mice. Insertion of the human DNA-PKcs(+/+) gene substantially increased the intrinsic radioresistance of the DNA-PKcs(-/-) tumor cells and substantially decreased tumor response to radiation in both nude and hypersensitive SCID mice. Tumor cell radiosensitivity was the major determinant of tumor response in nude mice. In SCID mice, both tumor cell sensitivity and radiation-induced stromal damage contributed to response. The relative contribution of host and tumor cell sensitivity on tumor response was unchanged for single doses of 1 x 15 and 6 x 3 Gy-fractionated dose irradiation.
Ogawa
Kazuhiko
K
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Boucher
Yves
Y
Kashiwagi
Satoshi
S
Fukumura
Dai
D
Chen
David
D
Gerweck
Leo E
LE
D000818:Animals; D048708:Cell Growth Processes / Q000528:radiation effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D009687:Nuclear Proteins / Q000235:genetics; D011836:Radiation Tolerance / Q000502:physiology*; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D014162:Transfection
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse