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Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro.

Ko SY, Ko HA, Shieh TM, Chang WC, Chen HI, Chang SS, Lin IH - PLoS ONE (2014)

Bottom 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Related in: MedlinePlus

RAGE antibody blocked AGE regulation.The use of RAGE antibody (10 ng/ml pretreatment for 1 hour) to block AGE conjugation resulted in a significant increase in the ERK phosphorylation, MMP2, and MMP9 due to AGEs. Compared with AGEs treatment (#), RAGE antibody blocked ERK phosphorylation, MMP2, and MMP9 (A and B) as well as cell migration (C).
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pone-0110542-g004: RAGE antibody blocked AGE regulation.The use of RAGE antibody (10 ng/ml pretreatment for 1 hour) to block AGE conjugation resulted in a significant increase in the ERK phosphorylation, MMP2, and MMP9 due to AGEs. Compared with AGEs treatment (#), RAGE antibody blocked ERK phosphorylation, MMP2, and MMP9 (A and B) as well as cell migration (C).

Mentions: RAGE antibodies (10 ng/ml pretreatment for 1 hour) were used to block AGE conjugation. Treatment with AGEs resulted in a significant increase in ERK phosphorylation and the expression of MMP2, and MMP9 (ERK: 1.31±0.03, P = 0.0008; MMP2: 1.38±0.04, P = 0.0005; MMP9: 1.32±0.09, P = 0.02). Compared to cells treated with AGEs alone, cells treated with both AGEs and RAGE antibody demonstrated significantly inhibited ERK phosphorylation (P = 0.009) as well as reduced expression of MMP2 (P = 0.05), and MMP9 (P = 0.0003) (Fig. 4 A and B). RAGE antibodies were also shown to suppress cell migration (Fig. 4C).


Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro.

Ko SY, Ko HA, Shieh TM, Chang WC, Chen HI, Chang SS, Lin IH - PLoS ONE (2014)

RAGE antibody blocked AGE regulation.The use of RAGE antibody (10 ng/ml pretreatment for 1 hour) to block AGE conjugation resulted in a significant increase in the ERK phosphorylation, MMP2, and MMP9 due to AGEs. Compared with AGEs treatment (#), RAGE antibody blocked ERK phosphorylation, MMP2, and MMP9 (A and B) as well as cell migration (C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199749&req=5

pone-0110542-g004: RAGE antibody blocked AGE regulation.The use of RAGE antibody (10 ng/ml pretreatment for 1 hour) to block AGE conjugation resulted in a significant increase in the ERK phosphorylation, MMP2, and MMP9 due to AGEs. Compared with AGEs treatment (#), RAGE antibody blocked ERK phosphorylation, MMP2, and MMP9 (A and B) as well as cell migration (C).
Mentions: RAGE antibodies (10 ng/ml pretreatment for 1 hour) were used to block AGE conjugation. Treatment with AGEs resulted in a significant increase in ERK phosphorylation and the expression of MMP2, and MMP9 (ERK: 1.31±0.03, P = 0.0008; MMP2: 1.38±0.04, P = 0.0005; MMP9: 1.32±0.09, P = 0.02). Compared to cells treated with AGEs alone, cells treated with both AGEs and RAGE antibody demonstrated significantly inhibited ERK phosphorylation (P = 0.009) as well as reduced expression of MMP2 (P = 0.05), and MMP9 (P = 0.0003) (Fig. 4 A and B). RAGE antibodies were also shown to suppress cell migration (Fig. 4C).

Bottom 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus