Wang Anxun, Zhang Bin, Huang Hongzhang, Zhang Leitao, Zeng Donglin, Tao Qian, Wang Jianguang, Pan Chaobin
Department of Oral and Maxillofacial Surgery, Guanghua College of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, PR China.
BMC Cancer. 2008 Jun 30;8:182. doi: 10.1186/1471-2407-8-182.
Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas.
Plasmids containing either MMP-2 siRNA or tissue inhibitor of metalloproteinase-2 (TIMP-2) cDNA were created and subsequently transfected into primary ameloblastoma cells. Zymography, RT-PCR, and Western blots were used to assess MMP-2 activity and expression of MMP-2 and TIMP-2, as well as protein levels.
Primary cultures of ameloblastoma cells expressed cytokeratin (CK) 14 and 16, and MMP-2, but only weakly expressed CK18 and vimentin. MMP-2 mRNA and protein levels were significantly inhibited by RNA interference (P < 0.05). Both MMP-2 siRNA and TIMP-2 overexpression inhibited MMP-2 activity and the in vitro invasiveness of ameloblastoma.
These results indicate that inhibition of MMP-2 activity suppresses the local invasiveness of ameloblastoma cells. This mechanism may serve as a novel therapeutic target in ameloblastomas pursuant to additional research.
成釉细胞瘤是具有局部侵袭性的牙源性肿瘤。本研究旨在探讨基质金属蛋白酶-2（MMP-2）在成釉细胞瘤侵袭性中的作用。
构建含有MMP-2小干扰RNA（siRNA）或金属蛋白酶组织抑制剂-2（TIMP-2）cDNA的质粒，随后将其转染至原代成釉细胞瘤细胞中。采用酶谱法、逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法评估MMP-2活性、MMP-2和TIMP-2的表达以及蛋白水平。
成釉细胞瘤细胞原代培养物表达细胞角蛋白（CK）14和16以及MMP-2，但仅微弱表达CK18和波形蛋白。RNA干扰显著抑制了MMP-2的mRNA和蛋白水平（P < 0.05）。MMP-2 siRNA和TIMP-2过表达均抑制了MMP-2活性和成釉细胞瘤的体外侵袭性。
这些结果表明，抑制MMP-2活性可抑制成釉细胞瘤细胞的局部侵袭性。根据进一步的研究，这一机制可能成为成釉细胞瘤新的治疗靶点。
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