Int J Med Sci 2020; 17(7):912-920. doi:10.7150/ijms.40864 This issue

Research Paper

CCR9 Promotes Migration and Invasion of Lung Adenocarcinoma Cancer Stem Cells

Lin Lu1,2*, Huan Du1*, Haowei Huang1*, Chenxi Wang1, Peipei Wang1, Zhiqiang Zha2, Yong Wu1,2, Xia Liu1,2, Chengyin Weng1,2, Xisheng Fang1,2, Baoxiu Li1,2, Haibo Mao1,2, Lina Wang1,2, Mingmei Guan1,2✉, Guolong Liu1,2✉

1. Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China, 510180
2. Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Lu L, Du H, Huang H, Wang C, Wang P, Zha Z, Wu Y, Liu X, Weng C, Fang X, Li B, Mao H, Wang L, Guan M, Liu G. CCR9 Promotes Migration and Invasion of Lung Adenocarcinoma Cancer Stem Cells. Int J Med Sci 2020; 17(7):912-920. doi:10.7150/ijms.40864. Available from https://www.medsci.org/v17p0912.htm

File import instruction

Abstract

Aim: CC chemokine receptor 9 (CCR9) interacts with its exclusive ligand CCL25, resulting in promoting tumor progression and metastasis. However, the effect and mechanisms of CCR9 on lung adenocarcinoma distant metastasis remain largely unknown. To preliminary clarify the underlying mechanisms, we investigate the correlation between CCR9 and ALDH1A1+cancer stem cells (CSCs), as well as the effect of CCR9 on the migration and invasion of CSCs.

Methods: Immunohistochemistry was performed to detect the expression of CCR9 in lung adenocarcinoma tissues. The correlations of CCR9 with distant metastasis and overall survival were investigated. Serial paraffin-embedded tissue blocks were used to detect ALDH1A1+CSCs expression. The correlations between CCR9 expression and ALDH1A1+CSCs were evaluated. We further studied the effect of CCR9/CCL25 on the migration and invasion of CSCs using transwell assays.

Results: There were positive correlations between CCR9 expression and distant metastasis, as well as poor overall survival. Patients with high CCR9 expression were more likely to develop distant metastasis and demonstrated poorer overall survival than patients with low CCR9 expression. In addition, there was positive correlation between the expression of CCR9 and ALDH1A1 in the same tumor microenvironment. ALDHhigh CSCs demonstrated enhanced expression of CCR9 than ALDHlow cells. Further transwell assays demonstrated that the numbers of CSCs migrated or invaded in response to CCL25 were more than that without CCL25 stimulation. Additional application of anti-CCR9 antibody reversed the CCL25-induced migration and invasion of CSCs.

Conclusions: In summary, our study demonstrated that CCR9/CCL25 promoted the migration and invasion of CSCs, which might contribute to distant metastasis and poor overall survival. Our findings provided evidence that CCR9/CCL25 could be used as novel therapeutic targets for lung adenocarcinoma.

Keywords: CCR9, lung adenocarcinoma, cancer stem cells, migration, invasion