Interleukin 6 receptor is an independent prognostic factor and a potential therapeutic target of ovarian cancer.
Interleukin 6 receptor is an independent prognostic factor and a potential therapeutic target of ovarian cancer.
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白细胞介素6受体是卵巢癌的独立预后因素和潜在的治疗靶点。
DOI：
10.1371/journal.pone.0118080
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kimura T
中科院分区：
文献类型：
--
作者：
Isobe A;Sawada K;Kinose Y;Ohyagi-Hara C;Nakatsuka E;Makino H;Ogura T;Mizuno T;Suzuki N;Morii E;Nakamura K;Sawada I;Toda A;Hashimoto K;Mabuchi S;Ohta T;Morishige K;Kurachi H;Kimura T
卵巢癌仍然是最致命的妇科癌症，针对这种悲惨疾病的新靶向分子疗法仍然具有挑战性。本研究分析了白细胞介素-6（IL-6）及其受体（IL-6 R）在卵巢癌组织中的表达模式，评价了这些表达对患者临床预后的影响，发现癌细胞中IL-6 R高水平表达而非IL-6表达是独立的预后因素。在使用卵巢细胞系的体外分析中，与原代正常卵巢表面上皮相比，7种细胞系中有6种（RMUG-S、RMG-1、OVISE、A2780、SKOV 3 ip 1和OVCAR-3）过表达IL-6 R，而7种细胞系中只有2种（RMG-1、OVISE）过表达IL-6，表明IL-6/IL-6 R信号传导在某些类型的卵巢癌细胞中以旁分泌方式发挥作用。从患者收集卵巢癌腹水，我们发现主要是M2极化巨噬细胞的原代CD 11b + CD 14+细胞是卵巢癌微环境中IL-6产生的主要来源。当CD 11b + CD 14+细胞与癌细胞共培养时，癌细胞的侵袭和增殖均被强烈地促进，并且这些促进作用几乎被抗IL-6 R抗体（托珠单抗）预处理完全抑制。本文提供的数据表明抗IL-6/IL-6 R疗法抑制卵巢癌腹膜扩散的基本原理，并代表抗IL-6 R疗法用于卵巢癌治疗的治疗潜力的证据。
Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment.
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影响因子：
8.8
作者：
Hall, M.;Gourley, C.;McNeish, I.;Ledermann, J.;Gore, M.;Jayson, G.;Perren, T.;Rustin, G.;Kaye, S.
通讯作者：
Kaye, S.
影响因子：
2.2
作者：
Kawamura, Kyoko;Komohara, Yoshihiro;Takeya, Motohiro
通讯作者：
Takeya, Motohiro
影响因子：
8.4
作者：
Oguro, Toshiki;Ishibashi, Kei;Kojima, Yoshiyuki
通讯作者：
Kojima, Yoshiyuki
影响因子：
6.4
作者：
ERROI, A;SIRONI, M;MANTOVANI, A
通讯作者：
MANTOVANI, A
影响因子：
11.5
作者：
Duan, Zhenfeng;Foster, Rosemary;Seiden, Michael V.
通讯作者：
Seiden, Michael V.