title: The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients.
abstract: BACKGROUND
  Osteolytic bone disease is a major hallmark in multiple myeloma (MM) progression and affects many patients. Several inflammatory cells are involved in MM progression. Among them, mast cells (MCs) accumulated in the bone marrow (BM) microenvironment are known to play an important role in the mechanism of neovascularization.
  
  
  METHODS
  In 52 newly diagnosed active MM patients, we measured BM MC density (MCD) using an immunohistochemical stain for tryptase, serum levels of matrix metalloproteinase-9 (MMP-9) and receptor activator of nuclear factor x03BA;B ligand (RANKL) by a solid-phase sandwich enzyme-linked immunosorbent assay, along with urine levels of N-terminal propeptide of procollagen type I (Ntx) by a competitive inhibition enzyme-linked immunosorbent assay, in various clinical stages and skeletal grades.
  
  
  RESULTS
  MCD, RANKL and Ntx were higher in MM patients. All values increased in association with both the clinical stage and skeletal grade. Furthermore, MCD correlated positively with MMP-9, RANKL and Ntx.
  
  
  CONCLUSIONS
  Our data suggest that MCs may contribute to osteolytic processes during MM progression. Although the major role of MCs in tumor progression is to enhance angiogenesis, it seems that they may affect MM bone disease and may secrete a plethora of mediators that may directly and indirectly have an impact on osteolysis.
authors.affiliation: Hematology Laboratory, University Hospital of Heraklion, Heraklion, Greece.
authors.forename: Rodanthi
authors.initials: R
authors.lastname: Vyzoukaki
authors.forename: George
authors.initials: G
authors.lastname: Tsirakis
authors.forename: Constantina A
authors.initials: CA
authors.lastname: Pappa
authors.forename: Maria
authors.initials: M
authors.lastname: Devetzoglou
authors.forename: Maria
authors.initials: M
authors.lastname: Tzardi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Alexandrakis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D001842:Bone and Bones / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002452:Cell Count; D060833:Cellular Microenvironment; D024042:Collagen Type I / Q000235:genetics / Q000652:urine; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000235:genetics / Q000473:pathology; D010015:Osteolysis, Essential / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000652:urine; D053245:RANK Ligand / Q000097:blood / Q000235:genetics; D053802:Tryptases / Q000097:blood / Q000235:genetics
chemical_list: D024042:Collagen Type I; D010455:Peptides; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D053802:Tryptases; D020780:Matrix Metalloproteinase 9