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Tissue inhibitor of metalloproteinase‐2 inhibits ameloblastoma growth in a new mouse xenograft disease model
Author(s) -
Zhang L.,
Zeng D.,
Huang H.,
Wang J.,
Tao Q.,
Pan C.,
Xu J.,
Zhang B.,
Wang A.
Publication year - 2010
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2009.00812.x
Subject(s) - ameloblastoma , transfection , nude mouse , in vivo , pathology , cancer research , matrix metalloproteinase , microbiology and biotechnology , chemistry , biology , medicine , gene , biochemistry , anatomy , maxilla
J Oral Pathol Med (2010) 39 : 94–102 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. Method: 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.