Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy.
Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy.
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DOI：
10.1186/s13048-015-0141-7
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发表时间：
2015-03-28
影响因子：
4
通讯作者：
Ratajczak MZ
中科院分区：
文献类型：
--
作者：
Gunjal PM;Schneider G;Ismail AA;Kakar SS;Kucia M;Ratajczak MZ
化疗和放射治疗的副作用之一是在各种组织和器官中诱导多种因子，为最初治疗后存活的癌细胞创造有利于转移的微环境。在本研究中，我们使用人卵巢癌细胞株A2780和免疫缺陷小鼠异种脂肪模型来测试布洛芬和地塞米松对改善治疗诱导的骨髓、肝脏和肺的促转移微环境的作用。在我们的研究中，我们发现，与未暴露于辐射或顺铂的动物相比，全身照射或顺铂给药增加了移植到免疫缺陷小鼠的人卵巢癌细胞的转移扩散。此外，从照射的小鼠骨髓、肺和肝脏获得的条件培养液吸引了人卵巢癌细胞，这种趋化活性在加热后被失活，这表明主要参与了多肽或多肽结合的趋化物质的作用。我们还观察到，如果暴露在从辐射小鼠骨髓中收集的细胞碎片中，人卵巢癌细胞增殖更好。最后，如果动物在放射治疗时给予非类固醇(布洛芬)或类固醇(泼尼松)抗炎药物治疗，由放化疗诱导的小鼠的促转移微环境得到显著改善。综上所述，我们认为放化疗诱导的、有利于转移的微环境在耐药癌细胞的转移中起着重要作用。这类细胞具有肿瘤干细胞的特性，具有高度的迁移性，通过非类固醇类药物进行简单、强化的抗炎治疗，以抑制放化疗后促转移因子的诱导，将是一种有趣的抗转移治疗方案。本文的在线版本(doi：10.1186/s13048-015-0141-7)包含补充材料，授权用户可以使用。
One of side effects of chemotherapy and radiotherapy is the induction of several factors in various tissues and organs that create a pro-metastatic microenvironment for cancer cells that survive initial treatment. In the present study, we employed human ovarian cancer cell line A2780 and immunodeficient mice xenogrfat model to test effect of both ibuprofen and dexamethasone to ameliorate the therapy-induced pro-metastatic microenvironment in bone marrow, liver, and lung. In our studies, we found that total body irradiation or administration of cisplatin increases the metastatic spread of human ovarian cancer cells transplanted into immunodeficient mice compared with animals unexposed to irradiation or cisplatin. Moreover, conditioned media harvested from irradiated murine bone marrow, lung, and liver chemoattracted human ovarian cancer cells, and this chemotactic activity was inactivated by heat, suggesting a major involvement of peptide or peptide-bound chemoattractants. We also observed that human ovarian cancer cells proliferate better if exposed to cell debris harvested from irradiated murine bone marrow. Finally, the pro-metastatic microenvironment in mice induced by radio- or chemotherapy was significantly ameliorated if animals were treated at the time of radiotherapy administration with non-steroid (ibuprofen) or steroid (prednisone) anti-inflammatory drugs. In summary, we propose that a radiochemotherapy-induced, pro-metastatic microenvironment plays an important role in the metastasis of cancer cells that are resistant to treatment. Such cells have characteristics of cancer stem cells and are highly migratory, and simple, intensive, anti-inflammatory treatment by non-steroid agents to suppress induction of pro-metastatic factors after radiochemotherapy would be an interesting anti-metastatic treatment alternative. The online version of this article (doi:10.1186/s13048-015-0141-7) contains supplementary material, which is available to authorized users.
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影响因子：
4
作者：
Brennecke P;Arlt MJ;Campanile C;Husmann K;Gvozdenovic A;Apuzzo T;Thelen M;Born W;Fuchs B
通讯作者：
Fuchs B
影响因子：
6.4
作者：
Janowska-Wieczorek, A;Wysoczynski, M;Ratajczak, MZ
通讯作者：
Ratajczak, MZ
影响因子：
7.5
作者：
Mukherjee S;Mazumdar M;Chakraborty S;Manna A;Saha S;Khan P;Bhattacharjee P;Guha D;Adhikary A;Mukhjerjee S;Das T
通讯作者：
Das T
影响因子：
8
作者：
Luker, K. E.;Lewin, S. A.;Mihalko, L. A.;Schmidt, B. T.;Winkler, J. S.;Coggins, N. L.;Thomas, D. G.;Luker, G. D.
通讯作者：
Luker, G. D.
影响因子：
4.8
作者：
Mizutani, Kosuke;Sud, Sudha;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.