Tissue inhibitor of metalloproteinase-2 inhibits ameloblastoma growth in a new mouse xenograft disease model.
BACKGROUND
Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to develop a new animal model of ameloblastoma and to address the role of tissue inhibitor of metalloproteinase-2 (TIMP-2) and matrix metalloproteinase-2 (MMP-2) in the growth and invasiveness of ameloblastomas.


METHODS
Donated fresh human ameloblastoma tissue was finely minced, screened, and subcutaneously implanted in three locations on each of 10 BALB/c-nu/nu nude mice. Newly established tumors on each mouse were injected with: (i) transfection reagent; (ii) liposome and transfection reagent; or (iii) liposome, transfection reagent, and the expression plasmid pcDNA3.1(+)/green fluorescent protein (GFP)-TIMP-2. Tumors were monitored for 5 weeks and excised for histopathology, RNA, and protein analyses.


RESULTS
The ameloblastoma xenografts were established with high frequency and contained a variety of typical features, validating this new model system. Xenografts injected with the TIMP-2 expression plasmid showed reduced growth, increased TIMP-2 mRNA and protein, and decreased MMP-2 protein compared with the control groups.


CONCLUSIONS
We successfully established a new experimental model of ameloblastoma consisting of subcutaneous human xenografts in nude mice. In addition, we demonstrated the successful introduction of the TIMP-2 gene in tumor xenograft cells in vivo, resulting in xenograft growth inhibition. This growth inhibition may have resulted from TIMP-2 overexpression specifically inhibiting MMP-2 protein expression and activity.
Zhang
L
L
Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Zeng
D
D
Huang
H
H
Wang
J
J
Tao
Q
Q
Pan
C
C
Xu
J
J
Zhang
B
B
Wang
A
A
D000328:Adult; D000564:Ameloblastoma / Q000188:drug therapy*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D040521:Subcutaneous Tissue / Q000601:surgery; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D061965:Matrix Metalloproteinase Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse