Department of Biotechnology, Kaohsiung Medical University, San-Ming District, Taiwan.
Oral Oncol. 2009 Sep;45(9):771-6. doi: 10.1016/j.oraloncology.2008.11.013. Epub 2009 Feb 11.
Lymph node metastasis is the hallmark of malignant neoplasms in patients of oral cancer, accounting for the poor diagnosis and reduced 5-year survival rate. Here we sought to identify cell motility-associated proteins of oral cancer by proteomic approach. We compared the proteomes of two oral cancer cells, CAL-27 and SAS, with the highest and the lowest migration potential, respectively, amongst six different oral cancer cell lines. Subsequent identification of differentially expressed proteins by LC-MS/MS and Western analysis revealed that SERPINB1 (serine protease inhibitor, clade B, member1) was highly expressed in CAL-27, the high-motility oral cancer cells. Semi-quantitative and real-time PCR further confirmed differential expression of SERPINB1 in these two cell lines at mRNA level. To verify the motility-promoting function of SERPINB1 in oral cancer cells, we showed that endogenous expression of SERPINB1 correlated positively with cell migration. Moreover, ectopic expression of SERPINB1 in oral cancer cells, SAS, Ca9-22, CAL-27 and HSC-3, increased cell migration by 25%, 52%, 90% and 100%, respectively. Finally, we found that the expression of SERPINB1 was significantly higher in 5 of 8 (62.5%) oral cancer tissues compared with the matched adjacent normal tissues. Besides, immunohistochemical results indicated over-expression of SERPINB1 in clinicopathologically invasive oral squamous cell carcinoma (OSCC) but not in normal oral mucosa (p<0.01). Together, our findings have provided a possible biomarker for oral cancer metastasis.
淋巴结转移是口腔癌患者恶性肿瘤的标志，导致诊断不佳和 5 年生存率降低。在这里，我们试图通过蛋白质组学方法鉴定口腔癌中的细胞迁移相关蛋白。我们比较了六种不同口腔癌细胞系中迁移潜力最高和最低的 CAL-27 和 SAS 口腔癌细胞的蛋白质组。通过 LC-MS/MS 和 Western 分析鉴定差异表达蛋白后发现，SERPINB1（丝氨酸蛋白酶抑制剂，B 族，成员 1）在 CAL-27（高迁移性口腔癌细胞）中高表达。半定量和实时 PCR 进一步证实了 SERPINB1 在这两种细胞系中的 mRNA 水平上的差异表达。为了验证 SERPINB1 在口腔癌细胞中的促迁移功能，我们表明内源性 SERPINB1 表达与细胞迁移呈正相关。此外，外源性表达 SERPINB1 在口腔癌细胞、SAS、Ca9-22、CAL-27 和 HSC-3 中分别增加了 25%、52%、90%和 100%的细胞迁移。最后，我们发现 8 例口腔癌组织中有 5 例（62.5%）的 SERPINB1 表达明显高于配对的相邻正常组织。此外，免疫组织化学结果表明，SERPINB1 在临床病理侵袭性口腔鳞状细胞癌（OSCC）中过度表达，但在正常口腔黏膜中不表达（p<0.01）。总之，我们的研究结果为口腔癌转移提供了一个可能的生物标志物。
