Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
J Oral Pathol Med. 2010 Apr;39(4):342-8. doi: 10.1111/j.1600-0714.2009.00836.x. Epub 2009 Dec 15.
Oral squamous cell carcinoma (OSCC) is one of the most malignant neoplasms worldwide, and the molecular mechanism of oral tumorigenesis is still unclear. Fatty-acid-binding protein 5 (FABP5) was found in our previous study to be upregulated in oral squamous cell carcinomas by proteomic analysis. The implications of FABP5 overexpression in oral cancer progression have not yet been elucidated.
In this study, the recombinant adeno-associated virus vectors were used to deliver and increase the expression of FABP5 in human OSCC cell lines. U6 promoter-driven short-hairpin RNA (shRNA)-triggered RNA interference was used to block FABP5 gene expression. Transwell Matrigel invasion assay, MTS cell proliferation assay, reverse transcription-polymerase chain reaction, Western blot, and gelatin zymography analysis were used to investigate the effects of FABP5 on cell invasion, growth, and matrix metalloproteinase (MMP) production.
Overexpression of FABP5 in oral cancer cells increased cell proliferation and invasiveness by increasing the expression of MMP-9. Silencing FABP5 with shRNA significantly suppressed cell proliferation, MMP-9 activities, and invasiveness.
Our study provides the first evidence that FABP5 expression modulated MMP-9 production and the invasive behavior of oral cancer cells and suggests that FABP5 may provide novel targets for therapeutic intervention.
口腔鳞状细胞癌(OSCC)是全球最恶性的肿瘤之一,口腔肿瘤发生的分子机制仍不清楚。我们之前的蛋白质组学分析发现脂肪酸结合蛋白 5(FABP5)在口腔鳞状细胞癌中上调。FABP5 过表达在口腔癌进展中的意义尚不清楚。
在本研究中,使用重组腺相关病毒载体在人 OSCC 细胞系中传递和增加 FABP5 的表达。U6 启动子驱动的短发夹 RNA(shRNA)触发 RNA 干扰用于阻断 FABP5 基因表达。Transwell Matrigel 侵袭实验、MTS 细胞增殖实验、逆转录-聚合酶链反应、Western blot 和明胶酶谱分析用于研究 FABP5 对细胞侵袭、生长和基质金属蛋白酶(MMP)产生的影响。
口腔癌细胞中 FABP5 的过表达通过增加 MMP-9 的表达增加了细胞增殖和侵袭性。用 shRNA 沉默 FABP5 显著抑制了细胞增殖、MMP-9 活性和侵袭性。
我们的研究首次提供了证据表明 FABP5 表达调节 MMP-9 的产生和口腔癌细胞的侵袭行为,并表明 FABP5 可能为治疗干预提供新的靶点。