title: Platelet factor-4 and its p17-70 peptide inhibit myeloma proliferation and angiogenesis in vivo.
abstract: BACKGROUND
  Angiogenesis plays an important role in the development of multiple myeloma (MM). The interaction between MM cells and the bone marrow microenvironment stimulates the proliferation and migration of endothelial progenitor cells (EPCs). Vascular endothelial growth factor (VEGF) contributes to the formation of new blood vessels by actively recruiting circulating EPCs. The production of proangiogenic and antiangiogenic factors is also dysregulated in MM. Platelet factor 4 (PF4) is a potent angiostatic cytokine that inhibits angiogenesis and tumor growth in several animal models.
  
  
  METHODS
  In this study, we stably transfected human myeloma cell lines with the PF4 gene or the sequence encoding its more potent p17-70 peptide and investigated the effects of PF4 and p17-70 on angiogenesis and tumor growth in vitro and in a SCID-rab myeloma model.
  
  
  RESULTS
  PF4 and p17-70 significantly attenuated VEGF production, both in vitro and in vivo. In a migration study using a Transwell system, PF4 or p17-70 markedly suppressed the migration of co-cultured human endothelial progenitor cells. PF4 or p17-70 also caused a significant reduction in microvessel densities in myeloma xenografts and markedly reduced the tumor volume in the SCID mice. Kaplan-Meier analysis demonstrated that PF4 and p17-70 significantly extended the overall survival of SCID mice bearing human myeloma xenografts.
  
  
  CONCLUSIONS
  Our findings indicate that PF4 or p17-70 could be valuable in combating multiple myeloma by disrupting tumor angiogenesis.
authors.affiliation: Department of Hematology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Rd, Shanghai 200003, China.
authors.forename: Longjiang
authors.initials: L
authors.lastname: Yang
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000401:mortality / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010978:Platelet Factor 4 / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D007147:Immunoglobulin Light Chains; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D010978:Platelet Factor 4