C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts
C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts
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C3a-C3aR信号通过调节癌相关成纤维细胞促进乳腺癌肺转移
DOI：
10.1186/s13046-019-1515-2
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发表时间：
2020-01
影响因子：
11.3
通讯作者：
Zhu Bo
中科院分区：
文献类型：
--
作者：
Shu Chi;Zha Haoran;Long Haixia;Wang XinXin;Yang Fei;Gao Jianbao;Hu Chunyan;Zhou Li;Guo Bo;Zhu Bo
背景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促进肿瘤进展。然而，C3a-C3aR信号在调节乳腺癌肺转移中的作用尚不清楚。结果C3a-C3aR信号转导通路促进了乳腺癌的转移。机制上，C3a-C3aR信号通过激活PI3K-AKT信号，促进CAF促转移细胞因子的分泌和细胞外基质成分的表达。基因或药物阻断C3aR信号通路可有效抑制小鼠乳腺癌的肺转移。结论C3a-C3aR信号通路促进了乳腺癌的转移。靶向C3aR信号通路是乳腺癌治疗的一种潜在的抗转移策略。
BackgroundMounting 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.MethodsWe 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.ResultsC3a-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.ConclusionsC3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1186/s13046-018-0767-6
发表时间：
2018-05-02
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Santolla MF;Lappano R;Cirillo F;Rigiracciolo DC;Sebastiani A;Abonante S;Tassone P;Tagliaferri P;Di Martino MT;Maggiolini M;Vivacqua A
通讯作者：
Vivacqua A
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
DOI：
10.4049/jimmunol.1501886
发表时间：
2016-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cho MS;Rupaimoole R;Choi HJ;Noh K;Chen J;Hu Q;Sood AK;Afshar-Kharghan V
通讯作者：
Afshar-Kharghan V