Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea.
Clin Exp Metastasis. 2011 Dec;28(8):803-10. doi: 10.1007/s10585-011-9411-y. Epub 2011 Jul 19.
Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been investigated using mice model having real-time condition of leucopenia. C57BL/6 mice were pre-exposed to a X-irradiation dose of 6 Gy on previous days 2, 5, 7, 10. Complete hematological parameters including lymphocyte subpopulation in blood and lung tissues were analyzed. Additionally, a group of mice including a non-irradiated group were inoculated with B16F10 cells (3 × 10(5)/200 μl) via tail vein at the same day, and lung metastasized colonies were compared among groups at day 14 of post-inoculation. We observed that (i) total leucocytes and platelet were gradually depleted by day 10; (ii) lung tissue showed gradual infiltration of leucocytes including neutrophils and lymphocytes; (iii) pulmonary colonies were maximum and minimum on day 5 and 10 respectively; (iv) lymphocyte subpopulation analysis showed most number of natural killer (NK) cells in lung tissues on day 10; (v) gene expression of platelet/endothelial cell adhesion molecule (PECAM) in lung tissues peaked on day 5. To sum-up the study, severity of leucopenia did not influence the incidence of metastasis but blood platelets and microenvironment alteration of targeting tissue may be responsible factors for lung metastasis in our experimental model.
放射治疗会对骨髓等正常组织产生非靶向效应。因此，电离辐射引起的微环境改变可能会影响动态的宿主-癌症生态系统，从而影响包括转移在内的癌症行为。在此，我们使用实时白细胞减少症模型的小鼠模型研究了高剂量照射后肺转移的发生率。C57BL/6 小鼠在之前的第 2、5、7、10 天预先接受 6Gy 的 X 射线照射。分析了血液和肺部组织中包括淋巴细胞亚群在内的全血细胞参数。此外，一组包括未照射组的小鼠在同一天通过尾静脉接种 B16F10 细胞（3×10(5)/200μl），并在接种后第 14 天比较各组的肺转移菌落。我们观察到：（i）总白细胞和血小板在第 10 天逐渐耗尽；（ii）肺组织逐渐浸润白细胞，包括中性粒细胞和淋巴细胞；（iii）肺部菌落在第 5 天和第 10 天分别达到最大值和最小值；（iv）淋巴细胞亚群分析显示第 10 天肺部组织中自然杀伤（NK）细胞数量最多；（v）肺部组织中血小板/内皮细胞黏附分子（PECAM）的基因表达在第 5 天达到峰值。总之，本研究表明白细胞减少症的严重程度并不影响转移的发生率，但血小板和靶向组织微环境的改变可能是我们实验模型中肺转移的重要因素。
