Endothelial cells promote triple-negative breast cancer cell metastasis via PAI-1 and CCL5 signaling.
Endothelial cells promote triple-negative breast cancer cell metastasis via PAI-1 and CCL5 signaling.
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内皮细胞通过 PAI-1 和 CCL5 信号传导促进三阴性乳腺癌细胞转移。
DOI：
10.1096/fj.201700237rr
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Guan Xiaoxiang
中科院分区：
文献类型：
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作者：
Zhang Wenwen;Xu Jing;Fang Hehui;Tang Lin;Chen Weiwei;Sun Qian;Zhang Qun;Yang Fang;Sun Zijia;Cao Lulu;Wang Yucai;Guan Xiaoxiang
Endothelial cells (ECs) in the tumor microenvironment have been reported to play a more active role in solid tumor growth and metastatic dissemination than simply providing the physical structure to form conduits for blood flow; however, the involvement of ECs in the process of triple‐negative breast cancer (TNBC) metastasis has not been addressed. Here, we demonstrate that ECs—when mixed with TNBC cells—could increase TNBC cell metastatic potency. After treatment with TGF‐p to induce endothelial‐mesenchymal transition (EMT), TNBC cells could produce plasminogen activator inhibitor‐1 (PAI‐1) and stimulate the expression and secretion of the che‐ mokine, CCL5, from ECs, which then acts in a paracrine fashion on TNBC cells to enhance their migration, invasion, and metastasis. CCL5, in turn, accelerates TNBC cell secretion of PAI‐1 and promotes TNBC cell metastasis, thus forming a positive feedback loop. Moreover, this enhanced metastatic ability is reversible and dependent on CCL5 signaling via the chemokine receptor, CCR5. Of importance, key features of this pathway are manifested in patients with TNBC and in The Cancer Genome Atlas database. Taken together, our results suggest that ECs enhance EMT‐ induced TNBC cell metastasisviaPAI‐1 and CCL5 signaling and illustrate the potential of developing new PAI‐1‐ and CCL5‐targeting therapy for patients with TNBC.—Zhang, W., Xu, J., Fang, H., Tang, L., Chen, W., Sun, Q., Zhang, Q., Yang, F., Sun, Z., Cao, L., Wang, Y., Guan, X. Endothelial cells promote triple‐negative breast cancer cell metastasisviaPAI‐1 and CCL5 signaling. FASEB J. 32,276‐288 (2018). www.fasebj.org
