title: Annexin 1 released by necrotic human glioblastoma cells stimulates tumor cell growth through the formyl peptide receptor 1.
abstract: Highly malignant human gliomas overexpress the G-protein-coupled chemoattractant receptor formyl peptide receptor (FPR1), which promotes tumor progression when activated. Our previous studies demonstrated that necrotic glioblastoma cells release chemotactic agonist(s) that activate FPR1 on viable tumor cells. In the present study, we identified an FPR1 agonist released by necrotic human glioblastoma cells. Necrotic tumor cell supernatant (NecSup) contained Annexin 1 (Anx A1), a chemotatic polypeptide agonist for FPR1. Immunoabsorption of Anx A1 with a specific antibody markedly reduced the chemotactic activity of NecSup for tumor cells and diminished its capacity to promote tumor cell growth, invasion, and colony formation on soft agar. In addition, Anx A1 was present in tumor xenografts formed by human glioblastoma cells in nude mice. Anx A1 knockdown significantly reduced the tumorigenicity of glioblastoma cells in nude mice, but FPR1/Anx A1 double knockdown diminished tumor growth even further. The clinical relevance of Anx A1 in gliomas was supported by the observation that Anx A1 was more highly expressed in poorly differentiated human primary gliomas compared with lower grade tumors. Our study implicates Anx A1 as a major component in necrotic tumor cell-derived stimulants of the growth of glioblastoma via the activation of FPR1.
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland; College of Marine Life Sciences, Ocean University of China, Qingdao, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yao
authors.forename: Yifang
authors.initials: Y
authors.lastname: Ping
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Senlin
authors.initials: S
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Haiwei
authors.initials: H
authors.lastname: Mou
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.forename: Xiuwu
authors.initials: X
authors.lastname: Bian
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Ming Wang
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002633:Chemotaxis / Q000502:physiology; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D044042:Receptors, Formyl Peptide / Q000819:agonists*; D014183:Transplantation, Heterologous
chemical_list: D017305:Annexin A1; C469986:FPR1 protein, human; D009363:Neoplasm Proteins; D044042:Receptors, Formyl Peptide