BACKGROUND Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown. METHODS We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer. RESULTS C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models. CONCLUSIONS C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.

中文翻译：

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C3a-C3aR信号传导通过调节癌相关的成纤维细胞促进乳腺癌的肺转移。

背景技术越来越多的证据表明补体成分通过调节免疫抑制，血管生成或肿瘤细胞增殖来促进肿瘤进展。然而，C3a-C3aR信号传导在调节乳腺癌的肺转移中的作用仍然未知。方法我们进行了各种离体和体内分析。遗传和药理C3aR封锁模型用于研究C3a-C3aR在乳腺癌转移中的作用。结果CAF中的C3a-C3aR信号传导促进了乳腺癌的转移。在机械上，C3a-C3aR信号传导通过PI3K-AKT信号传导的激活来增加CAF的促转移细胞因子分泌和细胞外基质成分的表达。C3aR信号的遗传或药理学阻断有效抑制了小鼠模型中乳腺癌的肺转移。结论CAF中的C3a-C3aR信号传导促进了乳腺癌的转移。靶向C3aR信号传导是乳腺癌治疗的潜在抗转移策略。