Ko Shun-Yao, Ko Hshin-An, Shieh Tzong-Ming, Chang Weng-Cheng, Chen Hong-I, Chang Shu-Shing, Lin I-Hsuan
Graduate Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan, Taiwan; Innovate Research Center of Medicine, Chang Jung Christian University, Tainan, Taiwan.
Innovate Research Center of Medicine, Chang Jung Christian University, Tainan, Taiwan.
PLoS One. 2014 Oct 16;9(10):e110542. doi: 10.1371/journal.pone.0110542. eCollection 2014.
Advanced glycation end products (AGEs) are produced in an irreversible non-enzymatic reaction of carbohydrates and proteins. Patients with diabetes mellitus (DM) are known to have elevated AGE levels, which is viewed as a risk factor of diabetes-related complications. In a clinical setting, it has been shown that patients with oral cancer in conjunction with DM have a higher likelihood of cancer metastasis and lower cancer survival rates. AGE-RAGE (a receptor of AGEs) is also correlated with metastasis and angiogenesis. Recent studies have suggested that the malignancy of cancer may be enhanced by glyceraldehyde-derived AGEs; however, the underlying mechanism remains unclear. This study examined the apparently close correlation between AGE-RAGE and the malignancy of SAS oral cancer cell line. In this study, AGEs increased ERK phosphorylation, enhanced cell migration, and promoted the expression of RAGE, MMP2, and MMP9. Using PD98059, RAGE antibody, and RAGE RNAi to block RAGE pathway resulted in the inhibition of ERK phosphorylation. Cell migration, MMP2 and MMP9 expression were also reduced by this treatment. Our findings demonstrate the importance of AGE-RAGE with regard to the malignancy of oral cancer, and help to explain the poor prognosis of DM subjects with oral cancer.
晚期糖基化终末产物（AGEs）是由碳水化合物和蛋白质发生不可逆的非酶促反应产生的。已知糖尿病（DM）患者的AGE水平会升高，这被视为糖尿病相关并发症的一个危险因素。在临床环境中，已表明患有口腔癌且合并DM的患者发生癌症转移的可能性更高，癌症生存率更低。AGE受体（RAGE）也与转移和血管生成相关。最近的研究表明，甘油醛衍生的AGEs可能会增强癌症的恶性程度；然而，其潜在机制仍不清楚。本研究探讨了AGE-RAGE与SAS口腔癌细胞系恶性程度之间明显的相关性。在本研究中，AGEs增加了ERK磷酸化，增强了细胞迁移，并促进了RAGE、MMP2和MMP9的表达。使用PD98059、RAGE抗体和RAGE RNAi阻断RAGE途径导致ERK磷酸化受到抑制。这种处理也降低了细胞迁移、MMP2和MMP9的表达。我们的研究结果证明了AGE-RAGE在口腔癌恶性程度方面的重要性，并有助于解释患有口腔癌的DM患者预后不良的原因。
