School of Stomatology, Lanzhou University, Gansu, China.
J Oral Pathol Med. 2011 Nov;40(10):762-8. doi: 10.1111/j.1600-0714.2011.01051.x. Epub 2011 Jun 21.
Patients with mucoepidermoid carcinoma exhibit poor long-term prognosis because of the lack of therapeutic strategies that effectively block tumor progression. We have previously characterized the Ms cells as a highly metastatic mucoepidermoid carcinoma cell line that expresses high levels of transforming growth factor β1 (TGF-β1). Here, we studied the effect of suppressing TGF-β1 by RNA silencing on the invasive and metastatic potential of mucoepidermoid carcinoma.
Cell motility, substratum adhesion, and transmembrane invasion were estimated by migration, matrigel adhesion, and matrigel invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 activity were determined using gelatin gel zymography. Balb/c nu/nu nude mice lung metastatic model was used to test the metastatic ability of the Ms cells. Lung metastatic tumors were experimentally induced by mice tail vein inoculation of cancer cells.
TGF-β1 silencing inhibits cell motility, substratum adhesion, and transmembrane invasion. In vivo, a significant decrease in lung metastasis was observed when mice received tail vein injections of TGF-β1-silenced mucoepidermoid carcinoma cells, as compared to controls.
These results unveil a critical role for TGF-β1 in the progression of mucoepidermoid carcinomas and suggest that patients with this malignancy may benefit from therapeutic inhibition of the effectors of the TGF-β1 pathway.
由于缺乏有效阻止肿瘤进展的治疗策略，黏液表皮样癌患者的长期预后较差。我们之前已经将 Ms 细胞鉴定为一种具有高转移性的黏液表皮样癌细胞系，其表达高水平的转化生长因子β1（TGF-β1）。在这里，我们研究了通过 RNA 干扰抑制 TGF-β1对黏液表皮样癌侵袭和转移潜能的影响。
通过迁移、基质胶黏附、基质胶侵袭试验评估细胞迁移性、基质黏附性和跨膜侵袭性。使用明胶酶谱法测定基质金属蛋白酶（MMP）-2 和 MMP-9 的活性。使用 Balb/c nu/nu 裸鼠肺转移模型来测试 Ms 细胞的转移能力。通过尾静脉接种癌细胞来实验性诱导小鼠肺转移瘤。
TGF-β1 沉默抑制细胞迁移性、基质黏附性和跨膜侵袭性。体内实验中，与对照组相比，接受尾静脉注射 TGF-β1 沉默的黏液表皮样癌细胞的小鼠肺转移明显减少。
这些结果揭示了 TGF-β1 在黏液表皮样癌进展中的关键作用，并提示患有这种恶性肿瘤的患者可能受益于 TGF-β1 通路效应物的治疗抑制。
