Stromal cells promote bone invasion by suppressing bone formation in ameloblastoma

Histopathology. 2008 Oct;53(4):458-67. doi: 10.1111/j.1365-2559.2008.03127.x.

Abstract

Aims: To study the stromal variation and role of stromal-tumour cell interaction in impaired bone formation as well as enhanced bone resorption in ameloblastoma.

Methods and results: Four types of stroma were observed histologically; fibrous, desmoplastic, myxoid and myxoid with hyalinization. Osteoblast and osteoclast were counted using haematoxylin and eosin sections and immunohistochemistry with CD68. After histomorphometric analysis, only fibrous and myxoid types of stroma were distinctly identified. Secreted frizzled-related peptide (sFRP)-2, transforming growth factor-beta 1 and receptor activator of nuclear factor-kappaB ligand (RANKL) revealed strong expression in myxoid type compared with the normal stroma. Bone morphogenetic protein (BMP)-2 was negative in myxoid type, but positive in normal stroma. Fibrous-type stroma showed weak expression of all antigens except RANKL compared with myxoid type.

Conclusions: The results suggest that stroma does not act only in bone resorption, but also in the suppression of new bone formation. sFRP-2 is the main factor for impaired bone formation. The expression of markers related to osteoclastogenesis and suppression of osteoblast formation is higher in myxoid-type than in fibrous-type stroma. Tumour cells create a favourable environment for impaired bone formation by secreting sFRP-2 as well as bone resorption by secreting RANKL and interleukin-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ameloblastoma / metabolism
  • Ameloblastoma / pathology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Bone Resorption / metabolism
  • Bone Resorption / pathology
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Jaw Neoplasms / metabolism
  • Jaw Neoplasms / pathology*
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis / physiology*
  • RANK Ligand / metabolism
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Interleukin-6
  • Membrane Proteins
  • RANK Ligand
  • SFRP2 protein, human