Abstract
Mechanism of CCL21/CCL19-CCR7 as a Key Regulatory Signaling Cassette for Non-Small Cell Lung Cancer Patients with Brain Metastasis
Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, 1Department of Oncology, Tianjin Key Laboratory of Cerebral Vascular and Neuro degenerative Diseases, Tianjin Neurosurgical Institute, Tianjin 300350, , 2Department of Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai, Tianjin 300193, 3Department of Clinical Laboratory, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Baodi, Tianjin 301800, China
Correspondence Address:
H. Ding, Department of Clinical Laboratory, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Baodi, Tianjin 301800, China, E-mail: 258860152@qq.com
To elucidate the molecular mechanism underlying the high metastasis rate of brain for non-small cell lung cancer patients and to establish a comprehensive differential gene profile for non-small cell lung cancer brain metastasis. The differentially expressed genes for non-small cell lung cancer brain metastasis patients were systematically investigated. The enriched biological processes and signaling pathways were explored. The protein-protein interaction network was constructed. Compared with primary non-small cell lung cancer, the brain metastasis patients demonstrated 352 differentially expressed genes with the majority as down-regulated ones (342) and 10 up-regulated ones. Meanwhile, C-C motif chemokine ligand 21, C-C motif chemokine ligand 19, deleted in malignant brain tumors 1 gene, tryptase alpha/beta 1, lactotransferrin, complement component 4 binding protein alpha, C-C motif chemokine ligand 14, C-X-C motif chemokine ligand 9, cluster of differentiation 79A as well as membrane spanning 4-domains A1 were significant and differentially expressed (all down-regulated). The genes of cluster including C-C motif chemokine ligand 21, C-C motif chemokine ligand 19 played a pivotal role in non-small cell lung cancer brain metastasis. The cytokines C-C motif chemokine ligand 19 and C-C motif chemokine ligand 21 as well as their closely associated receptors, C-C chemokine receptor 7 could be detected as high expression levels in non-small cell lung cancer cell line (A549). Inhibition of C-C motif chemokine ligand 19 and C-C motif chemokine ligand 21 as well as C-C chemokine receptor 7 using small interfering ribonucleic acid obviously repressed the cell invasion and metastasis but not for cell proliferation and apoptosis. Meanwhile, the procedure was independent of micro ribonucleic acid lethal-7a regulation. This study hypothesized an innovative signaling axis (C-C motif chemokine ligand 21/C-C motif chemokine ligand 19-C-C chemokine receptor 7) for non-small cell lung cancer brain metastasis and provided a beneficial strategy for better understanding the lung metastases in clinic.
