Wang Xiaolin, Li Ting, Cheng Yingying, Wang Pingzhang, Yuan Wanqiong, Liu Qiyao, Yang Fan, Liu Qiang, Ma Dalong, Ding Shigang, Wang Jun, Han Wenling
Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Laboratory of Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Oncoimmunology. 2019 Feb 18;8(5):e1577126. doi: 10.1080/2162402X.2019.1577126. eCollection 2019.
CYTL1 is a novel cytokine that was first identified in CD34 hematopoietic cells. We previously prepared recombinant CYTL1 and verified that it chemoattracted human monocytes via the CCR2/ERK pathway. It has been reported that CYTL1 plays contradictory roles in neuroblastoma and lung cancer. We found that the expression level of CYTL1 was notably decreased and it was hypermethylated in various tumors, including breast and lung cancer, by bioinformatics analyses. After validating the expression of CYTL1 in lung cancer, we identified that CYTL1 exerted no obvious effect on tumor cell proliferation but inhibited their migration and invasion, and these effects were accompanied by decreasing STAT3 phosphorylation, using recombinant CYTL1 and CYTL1-overexpressing tumor cell lines. Furthermore, we constructed experimental and spontaneous metastasis models of breast cancer in BALB/c mice and found that CYTL1 significantly inhibited tumor metastasis . In summary, CYTL1 is a cytokine with tumor-suppressing characteristics that inhibits tumor metastasis and STAT3 phosphorylation in multiple types of tumors.
CYTL1是一种首次在CD34造血细胞中被鉴定出的新型细胞因子。我们之前制备了重组CYTL1,并证实它通过CCR2/ERK途径趋化人单核细胞。据报道,CYTL1在神经母细胞瘤和肺癌中发挥着相互矛盾的作用。通过生物信息学分析,我们发现CYTL1的表达水平在包括乳腺癌和肺癌在内的各种肿瘤中显著降低且发生了高甲基化。在验证CYTL1在肺癌中的表达后,我们使用重组CYTL1和过表达CYTL1的肿瘤细胞系确定,CYTL1对肿瘤细胞增殖没有明显影响,但抑制其迁移和侵袭,并且这些作用伴随着STAT3磷酸化的降低。此外,我们构建了BALB/c小鼠乳腺癌的实验性和自发性转移模型,发现CYTL1显著抑制肿瘤转移。总之,CYTL1是一种具有肿瘤抑制特性的细胞因子,可抑制多种类型肿瘤的转移和STAT3磷酸化。