Influence of tumor cell and stroma sensitivity on tumor response to radiation
Influence of tumor cell and stroma sensitivity on tumor response to radiation
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DOI：
10.1158/0008-5472.can-06-4498
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发表时间：
2007-05-01
期刊：
影响因子：
11.2
通讯作者：
Gerweck, Leo E.
中科院分区：
文献类型：
--
作者：
Ogawa, Kazuhiko;Boucher, Yves;Gerweck, Leo E.
在这项研究中，我们评估的作用，肿瘤细胞和肿瘤间质的敏感性作为辐射诱导的肿瘤生长延迟的决定因素。用DNA双链断裂修复缺陷的DNA-PKcs（-/-）肿瘤细胞系及其放射抗性的DNA-PKcs（+/+）转染的对应物在裸小鼠和超敏的严重联合免疫缺陷（SCID）小鼠中引发肿瘤。人DNA-PKcs（+/+）基因的插入显著增加了DNA-PKcs-/-肿瘤细胞的内在辐射抗性，并显著降低了裸鼠和超敏SCID小鼠中肿瘤对辐射的反应。肿瘤细胞的放射敏感性是裸鼠肿瘤反应的主要决定因素。在SCID小鼠中，肿瘤细胞敏感性和辐射诱导的基质损伤都有助于反应。1 × 15和6 × 3 Gy分次剂量照射后，宿主和肿瘤细胞敏感性对肿瘤反应的相对贡献没有变化。
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 inummodeficient (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.