Influence of the C5a-C5a receptor system on breast cancer progression and patient prognosis
Influence of the C5a-C5a receptor system on breast cancer progression and patient prognosis
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DOI：
10.1007/s12282-015-0654-3
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发表时间：
2016-11-01
期刊：
影响因子：
4
通讯作者：
Iwase, Hirotaka
中科院分区：
文献类型：
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作者：
Imamura, Takahisa;Yamamoto-Ibusuki, Mutsuko;Iwase, Hirotaka
新的证据表明，癌细胞激活了肿瘤组织中的补体系统，并从C5中释放出过敏性毒素C5a，这表明C5a是癌症微环境中的一个组成部分。为探讨C5a-C5aR系统在乳腺癌中的作用，探讨C5a-C5aR系统在乳腺癌中的表达与患者临床病理参数的关系以及C5a对BC细胞增殖的影响。免疫组织化学方法检测171例乳腺癌患者中22例(13%)BC细胞C5aR的表达，并与肿瘤较大、核分级和Ki-67标记指数高、有无淋巴结转移和临床分期有关。有趣的是，所有原位BC患者的BC细胞均为C5aR阴性，激素受体阴性即三阴BC患者的C5aR阳性率较高(38%)。转移淋巴结中12例(55%)为C5aR阳性，其中7例原发灶为C5aR阴性。C5aR阳性BC患者的生存率低于C5aR阴性BC患者。C5a以C5aR依赖的方式促进表达C5aR的三重阴性BC细胞的增殖，BC C5aR的表达与肿瘤的发展和患者不良预后的关系以及C5a对表达C5aR的BC细胞的促增殖作用提示C5a-C5aR系统与BC的进展密切相关。该系统可能成为治疗BC患者的新靶点，尤其是三阴性BC患者。
Emerging evidence has shown activation of the complement system in cancer tissues and anaphylatoxin C5a release from C5 by cancer cells, suggesting C5a as a component in the cancer microenvironment. We revealed aberrant expression of C5a receptor (C5aR) in various human cancers and C5a-elicited enhancement of C5aR-expressing cancer cell invasion.To explore an influence of the C5a-C5aR system in breast cancer (BC), we investigated BC C5aR expression in relation to clinicopathological parameters of the patients and an effect of C5a on BC cell proliferation.BC cell C5aR expression was observed immunohistochemically in 22 of 171 patients (13 %) and related to larger tumor size, higher nuclear grade and Ki-67 labeling index, presence of lymph node metastasis and advanced clinical stages. Interestingly, BC cells were C5aR-negative in all patients with BC in situ and C5aR-positive rate was high (38 %) in patients with hormone receptor-negative, namely triple-negative BC. For BC cells in metastasized lymph nodes, 12 of 22 patients (55 %) were C5aR-positive and included 7 patients with C5aR-negative BC in the primary site. Survival rate of patients with C5aR-positive BC was lower than that of patients with C5aR-negative BC. C5a enhanced proliferation of C5aR-expressing triple-negative BC cells in a C5aR-dependent manner.Relation of BC C5aR expression to tumor development and poor prognosis of the patients and proliferation enhancing effect of C5a on C5aR-expressing BC cells suggest that the C5a-C5aR system is closely associated with BC progression. This system may be a new target to treat BC patients, particularly with triple-negative BC.