Zhang Bin, Zhang Jin, Huang Hong-Zhang, Chen Wei-Liang, Tao Qian, Zeng Dong-Lin, Zhang Lei-Tao, Xu Jian-Hui
Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
J Oral Pathol Med. 2009 Oct;38(9):731-6. doi: 10.1111/j.1600-0714.2009.00771.x. Epub 2009 Mar 24.
Ameloblastoma is an odontogenic benign tumor characterized by local invasiveness and most of its local recurrences clinically result from local invasion. This study used matrix metalloproteinase-2 (MMP-2) inhibitor I (MMP-2I) to investigate the role played by MMP-2 activity in the local invasiveness of ameloblastoma.
The cells and xenografts of ameloblastoma were treated with MMP-2I and treatment group were compared with the control group. In vitro, the invasive activity of tumor cells was assayed in transwell cell culture chamber. Gelatinolytic activity of gelatinases and MMP-2/tissue inhibitor of matrix metalloproteinase (TIMP-2) protein expression was detected using gelatin zymography and flow cytometry. The cell viability and adhesion were evaluated using methyl thiazol tetrazolium. In vivo, bilateral subrenal capsule xenograft transplantation of ameloblastoma was performed in 10 nude mice and the invasion of ameloblastoma into the renal parenchyma was observed.
Active-MMP-2 of conditioned media was significantly lower in treatment group than in the control group. Accordingly, potential of in vitro cell invasion, adhesion and in vivo tumor invasion were also significantly lower in the treatment group than in the control group.
Inhibitor of MMP-2 activity suppressed the local invasive capability of ameloblastoma by decreasing MMP-2 activity. MMP-2 activity is in relation with invasive capacity of ameloblastoma.
成釉细胞瘤是一种具有局部侵袭性的牙源性良性肿瘤,其大多数局部复发临床上是由局部侵袭引起的。本研究使用基质金属蛋白酶-2(MMP-2)抑制剂I(MMP-2I)来研究MMP-2活性在成釉细胞瘤局部侵袭中所起的作用。
用MMP-2I处理成釉细胞瘤的细胞和异种移植物,并将治疗组与对照组进行比较。在体外,在Transwell细胞培养小室中测定肿瘤细胞的侵袭活性。使用明胶酶谱法和流式细胞术检测明胶酶的明胶水解活性以及MMP-2/基质金属蛋白酶组织抑制剂(TIMP-2)蛋白表达。使用噻唑蓝评估细胞活力和黏附力。在体内,对10只裸鼠进行成釉细胞瘤双侧肾包膜下异种移植,并观察成釉细胞瘤向肾实质的侵袭情况。
治疗组条件培养基中的活性MMP-2明显低于对照组。相应地,治疗组的体外细胞侵袭、黏附潜力以及体内肿瘤侵袭也明显低于对照组。
MMP-2活性抑制剂通过降低MMP-2活性抑制了成釉细胞瘤的局部侵袭能力。MMP-2活性与成釉细胞瘤的侵袭能力有关。