当前位置: X-MOL 学术J. Exp. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Resolvins suppress tumor growth and enhance cancer therapy
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2018-01-02 , DOI: 10.1084/jem.20170681
Megan L. Sulciner 1, 2, 3 , Charles N. Serhan 4 , Molly M. Gilligan 1, 2, 3 , Dayna K. Mudge 1, 2, 3 , Jaimie Chang 1, 2, 3 , Allison Gartung 1, 2, 3 , Kristen A. Lehner 1, 2, 3 , Diane R. Bielenberg 5 , Birgitta Schmidt 6 , Jesmond Dalli 4 , Emily R. Greene 1, 2, 3 , Yael Gus-Brautbar 1, 2, 3 , Julia Piwowarski 1, 2, 3 , Tadanori Mammoto 5 , David Zurakowski 7, 8 , Mauro Perretti 9 , Vikas P. Sukhatme 3, 10 , Arja Kaipainen 11 , Mark W. Kieran 12, 13 , Sui Huang 14 , Dipak Panigrahy 1, 2, 3
Affiliation  

Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Thus, conventional cancer therapy is inherently a double-edged sword. In this study, we show that tumor cells killed by chemotherapy or targeted therapy (“tumor cell debris”) stimulate primary tumor growth when coinjected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin D1 (RvD1), RvD2, or RvE1. These mediators specifically inhibit debris-stimulated cancer progression by enhancing clearance of debris via macrophage phagocytosis in multiple tumor types. Resolvins counterregulate the release of cytokines/chemokines, including TNFα, IL-6, IL-8, CCL4, and CCL5, by human macrophages stimulated with cell debris. These results demonstrate that enhancing endogenous clearance of tumor cell debris is a new therapeutic target that may complement cytotoxic cancer therapies.



中文翻译:

Resolvins抑制肿瘤生长并增强癌症治疗

癌症疗法通过杀死肿瘤细胞来减轻肿瘤负担,但同时会产生肿瘤细胞碎片,从而刺激炎症和肿瘤生长。因此,传统的癌症疗法天生就是一把双刃剑。在这项研究中,我们显示当与亚阈值(非致瘤性)肿瘤细胞接种物共同注射时,通过触发巨噬细胞促磷脂酰丝氨酸释放后促炎性细胞因子释放,被化学疗法或靶向疗法杀死的肿瘤细胞(“肿瘤细胞碎片”)刺激了原发性肿瘤的生长。碎片刺激的肿瘤被抗炎药和可分解的脂质autacoids抑制,即resolvin D1(RvD1),RvD2或RvE1。这些介质通过在多种肿瘤类型中通过巨噬细胞吞噬作用增强碎片的清除,从而特异性地抑制碎片刺激的癌症进展。Resolvins通过受细胞碎片刺激的人类巨噬细胞来调节包括TNFα,IL-6,IL-8,CCL4和CCL5在内的细胞因子/趋化因子的释放。这些结果表明,增强内源性清除肿瘤细胞碎片是一种新的治疗靶标,可补充细胞毒性癌症治疗。

更新日期:2018-01-02
down
wechat
bug