The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients

Int Arch Allergy Immunol. 2015;168(4):263-8. doi: 10.1159/000443275. Epub 2016 Feb 20.

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology*
  • Bone and Bones / blood supply
  • Bone and Bones / metabolism
  • Bone and Bones / pathology*
  • Case-Control Studies
  • Cell Count
  • Cellular Microenvironment
  • Collagen Type I / genetics
  • Collagen Type I / urine
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mast Cells / metabolism
  • Mast Cells / pathology*
  • Matrix Metalloproteinase 9 / blood
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Multiple Myeloma / blood supply
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics
  • Multiple Myeloma / pathology*
  • Neoplasm Grading
  • Neoplasm Staging
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Osteolysis, Essential / blood
  • Osteolysis, Essential / diagnosis
  • Osteolysis, Essential / genetics
  • Osteolysis, Essential / pathology*
  • Peptides / genetics
  • Peptides / urine
  • RANK Ligand / blood
  • RANK Ligand / genetics
  • Tryptases / blood
  • Tryptases / genetics

Substances

  • Collagen Type I
  • Peptides
  • RANK Ligand
  • TNFSF11 protein, human
  • collagen type I trimeric cross-linked peptide
  • Tryptases
  • Matrix Metalloproteinase 9