title: Tumor self-seeding by circulating tumor cells in nude mouse models of human osteosarcoma and a preliminary study of its mechanisms.
abstract: OBJECTIVE
  The purpose of this study is to determine whether and how tumor self-seeding by circulating tumor cells (CTCs) plays a role in the initiation and progression of osteosarcoma.
  
  
  METHODS
  Two different nude mouse models of human osteosarcoma were established for detecting tumor self-seeding by fluorescently labeled CTCs. Various tumor growth indicators were quantitated for seeded and unseeded groups. Growth mechanisms were characterized using cell proliferation assays and immunohistochemical staining. Conditioned media of primary osteosarcoma cells was characterized in a Transwell migration assay and enzyme-linked immunosorbent assay. The effect of cytokines secreted by primary tumor cells was verified by small interfering RNA and recombinant human cytokine experiments.
  
  
  RESULTS
  Red fluorescent protein-labeled CTCs seeded primary tumors in both models. Seeded primary tumors groups grew faster than control groups (P < 0.05), which was partially attributed to the CTCs having a higher proliferation rate and higher vascular endothelial growth factor expression after self-seeding. Conditioned media of primary osteosarcoma cells attracted CTCs, through an IL-6-dependent mechanism.
  
  
  CONCLUSIONS
  CTC tumor self-seeding occurs in osteosarcoma and promotes the growth of primary osteosarcoma. CTCs appear to be recruited by cytokines secreted by primary osteosarcoma cells, particularly IL-6.
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.forename: Kuo
authors.initials: K
authors.lastname: Jiang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wen
authors.forename: Baoan
authors.initials: B
authors.lastname: Ma
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Fan
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009366:Neoplasm Seeding; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D015850:Interleukin-6; D008164:Luminescent Proteins; D034741:RNA, Small Interfering; D019947:Receptors, Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D000097573:Red Fluorescent Protein