Proton irradiation augments the suppression of tumor progression observed with advanced age.
Proton irradiation augments the suppression of tumor progression observed with advanced age.
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DOI：
10.1667/rr13538.1
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发表时间：
2014-03
影响因子：
3.4
通讯作者：
Hlatky L
中科院分区：
文献类型：
--
作者：
Beheshti A;Peluso M;Lamont C;Hahnfeldt P;Hlatky L
由于离子束放射治疗的物理优势，质子辐射比标准伽马辐射更能改善肿瘤靶向性。我们实验室的最新研究表明，除了这些靶向优势之外，质子照射还可以抑制对影响癌症进展的“标志”过程至关重要的血管生成和免疫因子，从而调节肿瘤的发展。除了质子的治疗用途之外，高能质子构成了银河宇宙射线的主要成分，因此是太空飞行致癌风险的考虑因素。鉴于质子照射调节已知随着衰老而减少的基本生物过程（例如血管生成和免疫原性），我们研究了质子照射如何影响肿瘤进展作为宿主年龄的函数，这是一个具有治疗和致癌作用的问题。将小鼠 Lewis 肺癌 (LLC) 细胞注射到同系青少年（68 天）与年老（736 天）C57BL/6 小鼠（有或没有同时照射）后，跟踪肿瘤滞后时间和生长动态。与青春期小鼠相比，老年小鼠的肿瘤生长受到抑制。这些差异通过质子辐照（1 GeV）进一步调节，在年老小鼠生长的肿瘤中抑制作用增强，且显着的辐射改变分子指纹明显。通过全局转录组分析，TGFβ1 和 TGFβ2 被确定为对观察到的肿瘤动态做出贡献的关键参与者。这些发现表明，老宿主支持肿瘤进展的能力降低，而质子照射可以进一步降低这种能力。
Proton radiation is touted for improved tumor targeting, over standard gamma radiation, due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory demonstrate that in addition to these targeting advantages, proton irradiation can inhibit angiogenic and immune factors critical to “hallmark” processes that impact cancer progression, thereby modulating tumor development. Outside the therapeutic utilization of protons, high-energy protons constitute a principal component of galactic cosmic rays and thus are a consideration in carcinogenesis risk for space flight. Given that proton irradiation modulates fundamental biological processes known to decrease with aging (e.g. angiogenesis and immunogenicity), we investigated how proton irradiation impacts tumor advancement as a function of host age, a question with both therapeutic and carcinogenesis implications. Tumor lag time and growth dynamics were tracked, after injection of murine Lewis lung carcinoma (LLC) cells into syngeneic adolescent (68 day) vs. old (736 day) C57BL/6 mice with or without coincident irradiation. Tumor growth was suppressed in old compared to adolescent mice. These differences were further modulated by proton irradiation (1 GeV), with increased inhibition and a significant radiation-altered molecular fingerprint evident in tumors grown in old mice. Through global transcriptome analysis, TGFβ1 and TGFβ2 were determined to be key players that contributed to the tumor dynamics observed. These findings suggest that old hosts exhibit a reduced capacity to support tumor advancement, which can be further reduced by proton irradiation.