Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth

  • Sci Adv. 2021 May 26;7(22):eabb5943. doi: 10.1126/sciadv.abb5943.
Fei Li  1 ,  Xufei Du  1 ,  Fen Lan  1 ,  Na Li  1 ,  Chao Zhang  1 ,  Chen Zhu  1 ,  Xiaohui Wang  1 ,  Yicheng He  1 ,  Zhehua Shao  1 ,  Haixia Chen  1 ,  Man Luo  1 ,  Wen Li  1 ,  Zhihua Chen  1 ,  Songmin Ying  2  3  4 ,  Huahao Shen  2  5
Affiliations
  • 1. Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • 2. Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China. [email protected] [email protected].
  • 3. International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China.
  • 4. Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 5. State Key Lab of Respiratory Disease, Guangzhou 510120, China.
PMID: 34039594 DOI: 10.1126/sciadv.abb5943
Abstract

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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