Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells
Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells
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DOI：
10.1016/j.cyto.2012.08.022
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发表时间：
2013-01-01
期刊：
影响因子：
3.8
通讯作者：
Pandey, B. N.
中科院分区：
文献类型：
--
作者：
Desai, Sejal;Kumar, Amit;Pandey, B. N.
细胞因子在肿瘤的发生、发展和发病机制中起着重要作用。越来越多的证据表明，不同起源的癌症的基础和应激诱导的细胞因子谱存在差异。然而，一个全面的调查后，急性和分次剂量的γ射线照射，其对旁观者细胞的生存的影响，各种肿瘤类型的细胞因子的特点是不为人所知的文献。在本研究中，我们已经评估了细胞因子分泌的人肿瘤细胞系（HT 1080，U373 MG，HT 29，A549和MCF-7）之前（基础）或之后的急性（2，6戈伊）和分次剂量（3 × 2戈伊）的γ-照射在培养基中从这些细胞获得的多重珠阵列/ELISA。此外，进行克隆形成测定以评估条件培养基（CM）对相应细胞的存活和生长的影响。基于对28种分析物的筛选，我们的结果表明，这些细胞系的基础概况在分泌因子的数量和幅度方面变化很大，这在MCF-7中是最小的。有趣的是，在所有细胞系的CM中发现TNF-α、IL-1 β、PDGF-AA、TGF-β 1、fractalkine、IL-8、VEGF和GCSF。然而，某些细胞因子的分泌是细胞系特异性的。此外，CM引起相应肿瘤细胞的克隆形成存活率增加（按HT 1080> U373 MG> HT 29> A549> MCF-7），这与它们的CM中的IL-1 β、IL-6、IL-8、GMCSF和VEGF的水平相关。照射后，大多数细胞因子的水平明显增加，并呈剂量依赖性。除MCF-7外，分级后收集的肿瘤细胞的辐照条件培养基（ICM）中细胞因子水平的倍数变化低于相应的急性剂量。有趣的是，在这些细胞系中，辐射诱导的细胞因子水平的倍数增加在A549细胞的ICM中最大。此外，用相应ICM处理的旁观者A549细胞显示克隆形成存活率的剂量依赖性降低。总之，本研究揭示了不同肿瘤细胞系的基础和辐射诱导的细胞因子谱的相似性和细微差异，以及其对各自旁观者细胞生长和存活的影响。这些发现可能为我们目前对细胞因子在癌症生物学中的作用的理解增加了一个新的维度。(C)2012爱思唯尔有限公司保留所有权利。
Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2,6 Gy) and fractionated doses (3 x 2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-alpha, IL-1 beta, PDGF-AA, TGF-beta 1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080 > U373MG > HT29 > A549> MCF-7), which was correlated with the levels of IL-1 beta, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent decrease in clonogenic survival. In conclusion, present study revealed the similarities and subtle differences in basal and radiation-induced cytokine profile of different tumor cell lines, and its influence on growth and survival of respective bystander cells. These findings may add a new dimension to our current understanding about role of cytokines in cancer biology. (C) 2012 Elsevier Ltd. All rights reserved.