Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth.
Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth.
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嗜酸性粒细胞炎症促进 CCL6 依赖性转移性肿瘤生长
DOI：
10.1126/sciadv.abb5943
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发表时间：
2021-05
期刊：
影响因子：
13.6
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Li F;Du X;Lan F;Li N;Zhang C;Zhu C;Wang X;He Y;Shao Z;Chen H;Luo M;Li W;Chen Z;Ying S;Shen H
嗜酸性粒细胞主要分泌CCL 6以促进肿瘤细胞迁移和转移形成。令人信服的证据表明，炎症成分有助于癌症的发展。然而，嗜酸性粒细胞，参与一些炎症性疾病，没有充分探讨在癌症转移。我们发现气道炎症性嗜酸性粒细胞增多和结肠炎症伴嗜酸性粒细胞浸润均与小鼠转移增加相关。嗜酸性粒细胞增多导致富含嗜酸性粒细胞的Cd 3 δ-IL-5转基因（IL-5 Tg）小鼠骨转移增加。我们还观察到胸膜转移癌患者的恶性胸腔积液中嗜酸性粒细胞增加。嗜酸性粒细胞通过分泌C-C基序趋化因子配体6（CCL 6）促进肿瘤细胞迁移和转移。IL-5转基因小鼠Ccl 6基因敲除可明显抑制骨转移。此外，抑制肿瘤细胞中的C-C趋化因子受体1（CCR 1，CCL 6的受体）减少肿瘤细胞迁移和转移。因此，我们的研究鉴定了嗜酸性粒细胞的CCL 6依赖性促转移活性，其可以通过靶向CCR 1来抑制，并代表了预防转移性疾病的方法。
Eosinophils primarily secrete CCL6 to promote tumor cell migration and metastasis formation. Compelling evidence suggests that inflammatory components contribute to cancer development. However, eosinophils, involved in several inflammatory diseases, were not fully explored in cancer metastasis. We show that airway inflammatory eosinophilia and colonic inflammation with eosinophil infiltration are both associated with increased metastasis in mice. Eosinophilia is responsible for increased bone metastasis in eosinophil-enriched Cd3δ-Il-5 transgenic (Il-5 Tg) mice. We also observe increased eosinophils in the malignant pleural effusion of cancer patients with pleural metastasis. Mechanistically, eosinophils promote tumor cell migration and metastasis formation through secreting C-C motif chemokine ligand 6 (CCL6). Genetic knockout of Ccl6 in Il-5 Tg mice remarkably attenuates bone metastasis. Moreover, inhibition of C-C chemokine receptor 1 (CCR1, the receptor of CCL6) in tumor cells reduces tumor cell migration and metastasis. Thus, our study identifies a CCL6-dependent prometastatic activity of eosinophils, which can be inhibited by targeting CCR1 and represent an approach to preventing metastatic disease.
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