Brain microvascular endothelium induced-annexin A1 secretion contributes to small cell lung cancer brain metastasis |
| |
| Institution: | 1. Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, China;2. Department of Neurosurgery, The First Hospital of China Medical University, China;3. Department of Medical Examination, Shengjing Hospital of China Medical University, China;1. Ann Romney Center for Neurologic Diseases, Brigham and Women''s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA;1. Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, People''s Republic of China;2. Department of Radiotherapy and Oncology, The Affiliated Hospital of Nantong University, Xisi Road No. 20, Nantong 226001, People''s Republic of China;3. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, People''s Republic of China;4. Department of Neurosurgery, The Affiliated Hospital of Nantong University, Xisi Road No. 20, Nantong 226001, People''s Republic of China;5. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province 226001, People''s Republic of China;6. Department of Pathology, The Affiliated Hospital of Nantong University, Xisi Road No. 20, Nantong 226001, People''s Republic of China;1. Department of Dermatology, Hospital Santa Casa de Curitiba, Paraná, Brazil;2. Department of Dermatology, Hospital Santa Casa de Porto Alegre, Rio Grande do Sul, Brazil;1. Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA;2. Lieber Institute for Brain Development, Baltimore, MD, USA;3. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA;4. Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine Translational Research Laboratories, Philadelphia, PA, USA;5. Department of Biomedical Sciences, Rowan University, Camden, NJ, USA;6. Department of Pharmacology, Uniformed Services University, Bethesda, MD, USA;1. Department of Bioregulation Sciences, Health Sciences Institute, Federal University of Bahia, UFBA, Brazil;2. Pharmacology Department, São Paulo Federal University, UNIFESP, Brazil;3. Graduate Program in Pharmacy, Federal University of Bahia, UFBA, Brazil;4. Pharmacology Department, Biomedical Sciences Institute, Federal University of Uberlândia, UFU, Brazil;1. PTSD Lab, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical College, China Medical University, Shenyang, PR China;2. Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands |
| |
| Abstract: | Small cell lung cancer is the most aggressive histologic subtype of lung cancer, with a strong predilection for metastasizing to brain early. However, the cellular and molecular basis is poorly known. Here, we provided evidence to reveal the role of annexin A1 in small cell lung cancer metastasis to brain. Firstly, the elevated annexin A1 serum levels in small cell lung cancer patients were associated with brain metastasis. The levels of annexin A1 were also upregulated in NCI-H446 cells, a small cell lung cancer cell line, upon migration into the mice brain. More interestingly, annexin A1 was secreted by NCI-H446 cells in a time-dependent manner when co-culturing with human brain microvascular endothelial cells, which was identified with the detections of annexin A1 in the co-cultured cellular supernatants by ELISA and western blot. Further results showed that blockage of annexin A1 in the co-cultured cellular supernatants using a neutralized antibody significantly inhibited NCI-H446 cells adhesion to brain endothelium and its transendothelial migration. Conversely, the addition of Ac2-26, an annexin A1 mimic peptide, enhanced these effects. Furthermore, knockdown of annexin A1 in NCI-H446 cells prevented its transendothelial migration in vitro and metastasis to mice brain in vivo. Our data showed that small cell lung cancer cell in brain microvasculature microenvironment could express much more annexin A1 and release it outside, which facilitated small cell lung cancer cell to gain malignant properties of entry into brain. These findings provided a potential target for the management of SCLC brain metastasis. |
| |
| Keywords: | Annexin A1 Small cell lung cancer Human brain microvascular endothelial cells Brain metastasis Blood–brain barrier |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
