Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour.
OBJECTIVE
Ameloblastoma is an odontogenic neoplasm with local invasiveness and recurrence. We have previously suggested that growth factors and matrix metalloproteinases (MMPs) influence ameloblastoma invasiveness. The aim was to study expression of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and growth factors in ameloblastoma.


RESULTS
Thirteen cases of solid/multicystic ameloblastoma were examined. As a control, calcifying cystic odontogenic tumour (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium was also studied. Immunohistochemistry detected MMPs, TIMPs and growth factors in ameloblastoma and CCOT. The labelling index (LI) of MMP-9 and TIMP-2 was significantly higher in ameloblastoma compared with CCOT. The LI of epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) was also increased in ameloblastoma. This neoplasm showed greater expression of MMPs, TIMPs and growth factors compared with CCOT. We then analysed these molecules in ameloblastoma cells and stroma. Ameloblastoma cells exhibited increased LI of MMP-1, -2 and EGFR. We found a positive correlation between EGF and TIMP-1, and between TGF-alpha and TIMP-2. It is known that signals generated by growth factors are transduced by the ERK pathway. Ameloblastoma stroma exhibited the phosphorylated (activated) form of ERK.


CONCLUSIONS
These results suggest an interplay involving growth factors MMPs and TIMPs that may contribute to ameloblastoma behaviour. Signals generated by this molecular network would be transduced by ERK 1/2 pathway.
Siqueira
Adriane S
AS
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Carvalho
Marcia R D
MR
Monteiro
Ana C D
AC
Freitas
Vanessa M
VM
Jaeger
Ruy G
RG
Pinheiro
Joao J V
JJ
D000564:Ameloblastoma / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007573:Jaw Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D018333:Odontogenic Cyst, Calcifying / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D016211:Transforming Growth Factor alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1