Association of expression of receptor for advanced glycation end products and invasive activity of oral squamous cell carcinoma
Association of expression of receptor for advanced glycation end products and invasive activity of oral squamous cell carcinoma
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DOI：
10.1159/000087910
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Kato, Y
中科院分区：
文献类型：
--
作者：
Bhawal, UK;Ozaki, Y;Kato, Y
目的：晚期糖基化终产物受体（receptor for advanced glycation end products，RECEPTOR）是近年来发现的一种调节肿瘤细胞侵袭和转移的因子。然而，在口腔鳞状细胞癌的发展和进展中的参与tumor还没有得到阐明。本研究探讨了10种口腔鳞状细胞癌细胞系（包括原发细胞系和转移细胞系）中Bcl-2蛋白的表达及其与侵袭和转移的关系。研究方法：采用逆转录-聚合酶链反应、反义硫代磷酸（S）-寡脱氧核苷酸检测、抗体制备、免疫组化染色、免疫印迹分析、迁移实验、体外侵袭实验和伤口愈合实验。结果如下：与正义S-寡脱氧核苷酸处理的细胞相比，用反义S-寡脱氧核苷酸处理的转移癌细胞的p53蛋白表达显著降低。迁移实验表明，经反义S-寡核苷酸处理的转移癌细胞的侵袭活性显著降低。类似地，在侵袭测定期间，随着加入反义S-寡脱氧核苷酸处理的细胞，侵袭细胞的数量也减少。伤口愈合试验表明，只有少数反义S-寡脱氧核苷酸处理的癌细胞迁移到刮擦区域，而正义S-寡脱氧核苷酸处理的细胞在转移细胞系的刮擦区域显示出许多出芽巢。免疫组化显示，口腔鳞状细胞癌细胞在肿瘤间质边缘常呈免疫阳性，而在正常粘膜基底细胞几乎不呈阳性。结论：这些结果表明，cDNA 3的表达似乎与口腔鳞状细胞癌的侵袭性密切相关，并代表了一个有前途的候选人，用于评估未来的治疗潜力，在治疗口腔癌患者。版权所有（C）2005 S. Karger AG，巴塞尔。
Objectives: The receptor for advanced glycation end products (RAGE) is a newly recognized factor regulating cancer cell invasion and metastasis. Nevertheless, the involvement of RAGE in the development and progression of oral squamous cell carcinomas has not been elucidated. This study investigated the expression of RAGE in ten oral squamous cell carcinoma cell lines including primary and metastatic cell lines and its association with invasion and metastasis. Methods: Reverse transcriptase-polymerase chain reaction, antisense phosphorothioate (S)-oligodeoxynucleotide assay, preparation of antibody, immunohistochemical staining, immunoblot analysis, migration assay, in vitro invasion assay, and wound-healing assay were used. Results: RAGE protein expression of metastatic cancer cells treated with RAGE antisense S-oligodeoxynucleotide was significantly reduced compared to that of sense S-oligodeoxynucleotide-treated cells. The migration assay showed that invasive activity was significantly reduced in metastatic cancer cells treated with RAGE antisense S-oligodeoxynucleotide. Similarly, during invasion assays, numbers of invading cells were also reduced with the addition of RAGE antisense S-oligodeoxynucleotide-treated cells. A wound-healing assay showed that only a few RAGE antisense S-oligodeoxynucleotide-treated cancer cells migrated into the scraped area, whereas sense S-oligodeoxynucleotide-treated cells showed many budding nests in the scraped area of the metastatic cell lines. Immunohistochemically, oral squamous cell carcinoma cells in the tumour mesenchymal border were often immunopositive, whereas basal cells in the normal mucosa were scarcely positive. Conclusions: These results suggest that RAGE expression appears to be closely associated with the invasiveness of oral squamous cell carcinoma and represents a promising candidate for assessing the future therapeutic potential in treating patients with oral carcinoma. Copyright (C) 2005 S. Karger AG, Basel.