Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model
Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model
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DOI：
10.1016/j.ijrobp.2013.08.044
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发表时间：
2013-12-01
影响因子：
7
通讯作者：
Madlambayan, Gerard J.
中科院分区：
文献类型：
--
作者：
Kane, Jonathan;Krueger, Sarah A.;Madlambayan, Gerard J.
用途：为了表征小鼠异位肿瘤模型中放射治疗（RT）后肿瘤微环境内骨髓（BM）衍生的造血干细胞和祖细胞（HSPCs）的募集情况：方法和材料：在C57 BL/6小鼠中建立刘易斯肺癌肿瘤，并在2天内以30戈伊剂量分2次照射。用正电子发射断层扫描/计算机断层扫描（PET/CT）对肿瘤进行成像，并每天用数字卡尺进行测量。通过免疫荧光染色和流式细胞术评估HSPC和骨髓单核细胞含量。肿瘤相关的HSPCs的功能进行了验证，在体外使用集落形成细胞测定和在体内抢救致命照射C57 BL/6 recipients.Results：照射显着降低肿瘤体积和肿瘤再生长率相比，non-radiated控制。在再生长的所有阶段，照射肿瘤中存在的CD 133（+）HSPC的数量高于未照射肿瘤。CD 11b（+）计数相似。PET/CT成像和基于标准化摄取值的生长速率分析表明，HSPC募集与照射后的再生长程度和瘤内细胞活性直接相关。骨髓来源的肿瘤相关HSPC成功地形成造血集落并植入辐射小鼠。最后，有针对性的治疗与小动物放射研究平台表明，本地化HSPC招聘到定义的肿瘤subsites暴露于radiation.Conclusions：Hypofractionated照射导致一个显着的和有针对性的招聘BM衍生的HSPCs，可能作为一种机制，以促进肿瘤再生长。这些数据首次表明，放射治疗调节再生肿瘤内的HSPC含量。(C)2013 Elsevier Inc.
Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model.Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients.Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133(+) HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b(+) counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation.Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors. (C) 2013 Elsevier Inc.