title: Stromal cells promote bone invasion by suppressing bone formation in ameloblastoma.
abstract: OBJECTIVE
  To study the stromal variation and role of stromal-tumour cell interaction in impaired bone formation as well as enhanced bone resorption in ameloblastoma.
  
  
  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.
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: G S A
authors.initials: GS
authors.lastname: Sathi
authors.forename: H
authors.initials: H
authors.lastname: Nagatsuka
authors.forename: R
authors.initials: R
authors.lastname: Tamamura
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Gunduz
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: R S
authors.initials: RS
authors.lastname: Rivera
authors.forename: N
authors.initials: N
authors.lastname: Nagai
mesh_terms: D000328:Adult; D000564:Ameloblastoma / Q000378:metabolism / Q000473:pathology*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007573:Jaw Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D000097382:CD68 Molecule; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015850:Interleukin-6; D008565:Membrane Proteins; D053245:RANK Ligand; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins