Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth.
Fei LiXufei DuFen LanNa LiChao ZhangChen ZhuXiaohui WangYicheng HeZhehua ShaoHaixia ChenMan LuoWen LiZhi-Hua ChenSongmin YingHuahao ShenPublished in: Science advances (2021)
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.
Keyphrases
- cell migration
- oxidative stress
- papillary thyroid
- liver fibrosis
- squamous cell carcinoma
- small cell lung cancer
- liver injury
- dendritic cells
- type diabetes
- high fat diet induced
- immune response
- skeletal muscle
- binding protein
- dna methylation
- regulatory t cells
- bone loss
- wild type
- insulin resistance
- chronic rhinosinusitis