Enhancement of cancer invasion and growth via the C5a-C5a receptor system: Implications for cancer promotion by autoimmune diseases and association with cervical cancer invasion
Enhancement of cancer invasion and growth via the C5a-C5a receptor system: Implications for cancer promotion by autoimmune diseases and association with cervical cancer invasion
复制标题
通过 C5a-C5a 受体系统增强癌症侵袭和生长：自身免疫性疾病促进癌症的影响以及与宫颈癌侵袭的关联
作者：
Masakazu Yoneda;Ryuji Imamura;H. Nitta;K. Taniguchi;F. Saito;K. Kikuchi;Hidenao Ogi;Takuya Tanaka;H. Katabuchi;H. Nakayama;T. Imamura
自身免疫性疾病是由免疫复合物诱导的补体系统激活和随后的炎症引起的。最近的研究揭示了自身免疫性疾病与癌症患者生存率下降之间的关联;然而，其潜在机制仍不清楚。C5 a-C5 a受体（C5 aR）系统已被证明可增强癌症活性并募集抑制抗肿瘤免疫应答的骨髓源性抑制细胞（MDSC）。Arthus反应是由免疫复合物激活补体系统引起的炎症，因此是自身免疫性疾病的模型。为了探索Arthus反应对癌症进展的影响，将小鼠癌细胞接种在同基因小鼠皮肤中，其中同时诱导Arthus反应。Arthus反应增强了C5 aR阳性癌细胞的侵袭和肿瘤生长，而不是对照细胞，并诱导MDSC募集。将C5 a刺激的C5 aR阳性癌细胞静脉注射到裸鼠中导致比注射未经处理的C5 aR阳性细胞和C5 a刺激的C5 aR阴性细胞更多的肺结节，支持C5 a-C5 aR介导的癌症生长增强。C5 aR在宫颈癌I期细胞中的表达显著高于CIN 3细胞，CIN 3细胞仍在上皮中。这些结果表明，C5 a-C5 aR系统的癌症促进作用可能是自身免疫性疾病癌症患者预后不良的基础，特别是在C5 aR阳性癌症患者中，并且可能与宫颈癌侵袭相关。C5 a-C5 aR系统增强癌细胞的侵袭和生长表明该系统是癌症治疗的可能靶点。
Autoimmune diseases are caused by immune complex-induced activation of the complement system and subsequent inflammation. Recent studies have revealed an association between autoimmune diseases and worse survival in patients with cancer; however, the underlying mechanism is still unknown. The C5a-C5a receptor (C5aR) system has been shown to enhance cancer activity and recruit myeloid-derived suppressor cells (MDSCs) that suppress the anti-tumor immune response. The Arthus reaction is inflammation caused by complement system activation by the immune complex and thus is a model of autoimmune diseases. To explore the effect of the Arthus reaction on cancer progression, mouse cancer cells were inoculated in syngeneic mouse skin, where the Arthus reaction was induced simultaneously. The Arthus reaction enhanced invasion and tumor growth of C5aR-positive cancer cells, but not control cells, and induced MDSC recruitment. Intravenous injection of C5a-stimulated C5aR-positive cancer cells into nude mice resulted in more lung nodules than injection of nontreated C5aR-positive cells and C5a-stimulated C5aR-negative cells, supporting C5a-C5aR-mediated enhancement of cancer growth. C5aR expression in uterine cervical carcinoma stage I cells, which invade into the deeper tissues, was significantly higher than that in CIN3 cells, which remain in the epithelium. These results indicate that cancer promotion by the C5a-C5aR system may underlie poor prognosis in cancer patients with autoimmune diseases, particularly in patients with C5aR-positive cancer, and may be associated with cervical cancer invasion. The enhancement of cancer cell invasion and growth by the C5a-C5aR system suggests that this system is a possible target of cancer therapy.
影响因子：
6
作者：
Markiewski, Maciej M.;Lambris, John D.
通讯作者：
Lambris, John D.
补体亚型 C4A 或 C4B 的遗传缺陷预示着转移性肾细胞癌的生存率提高。
DOI：
10.1016/j.juro.2008.11.013
发表时间：
2009
期刊：
The Journal of urology
影响因子：
--
作者：
Zafar,GhazalI;Grimm,ElizabethA;Wei,Wei;Johnson,MarcellaM;Ellerhorst,JulieA
通讯作者：
Ellerhorst,JulieA