Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation
Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation
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DOI：
10.1016/j.mrfmmm.2014.03.004
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发表时间：
2014-05-01
影响因子：
2.3
通讯作者：
Pandey, Badri N.
中科院分区：
文献类型：
--
作者：
Desai, Sejal;Kobayashi, Alisa;Pandey, Badri N.
辐射诱导的旁观者效应（RIBE）的大多数研究都集中在了解正常细胞群中旁观者细胞对辐射信号的反应所观察到的辐射生物学变化，从而影响辐射风险评估。然而，关于RIBE与癌症放疗相关的报道，特别是研究癌症和正常细胞之间的双向和交叉旁观者通信的报道有限。因此，在本研究中，我们采用共培养的方法，研究了质子微束照射后肺癌细胞（A549）和正常细胞（WI38）之间的旁观者串扰，使用γ - h2ax聚焦荧光作为DNA双链断裂（DSBs）的测量。我们观察到，在A549-A549共培养中，辐照的A549细胞对旁观的A549细胞产生损伤作用，这种损伤作用是通过间隙连接细胞间通讯（GJIC）介导的。然而，在A549-WI38共培养中，辐照的A549不影响旁观者的WI38细胞。相反，旁观者WI38细胞在辐照的A549细胞中诱导了不依赖于GJIC的反向保护性信号传导（拯救效应）。另一方面，在WI38细胞辐照下，旁观细胞（A549或WI38）均未显示出γ - h2ax灶的显著增加。观察到的肿瘤和正常细胞之间的旁观者信号可能对癌症放疗的治疗结果有潜在的影响。(C) 2014 Elsevier B.V.版权所有
Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using gamma-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549-A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549-WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in gamma-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy. (C) 2014 Elsevier B.V. All rights reserved.