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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

Inhibition of cell proliferation by AGEs.SAS cells were treated with AGEs (0–400 µg/ml) or BSA (0–400 µg/ml) for 24 to 48 hours. The number of cells and proliferation were detected using trypan blue dye exclusion (A) and a WST-1 assay (B). AGEs significantly reduced the number of cells; BSA (as a negative control) increased viability (A). AGEs also inhibited cell proliferation (B). Treatment with AGEs (400 µg/ml; 0–4 hours) enhanced cell migration, while treatment with BSA did not (C).
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pone-0110542-g001: Inhibition of cell proliferation by AGEs.SAS cells were treated with AGEs (0–400 µg/ml) or BSA (0–400 µg/ml) for 24 to 48 hours. The number of cells and proliferation were detected using trypan blue dye exclusion (A) and a WST-1 assay (B). AGEs significantly reduced the number of cells; BSA (as a negative control) increased viability (A). AGEs also inhibited cell proliferation (B). Treatment with AGEs (400 µg/ml; 0–4 hours) enhanced cell migration, while treatment with BSA did not (C).

Mentions: We first assessed the influence of AGEs on cell viability. SAS cells were treated with AGEs (0–400 µg/ml) or BSA (0–400 µg/ml) for 24 or 48 hours, whereupon the number of cells and proliferation rate were determined according to trypan blue dye exclusion (Fig. 1A) and WST-1 assays (Fig. 1B). Compared with control cells, AGE treated cells showed a significant reduction in number of cells (24 hours AGEs 100: 2.88±0.16, P = 0.006; AGEs 200: 2.6±0.25, P = 0.008; AGEs 400: 1.85±0.05, P <0.0001; 48 hours AGEs 100: 3.1±0.18, P = 0.05; AGEs 200: 2.57±0.17, P = 0.01; AGEs 400: 2.03±0.08, P = 0.003). In contrast, BSA was shown to increase the number of cells (as a negative control, 24 hours: 4.77±0.32, NS; 48 hours: 9.25±0.35, P = 0.0004) (Fig. 1A). In addition, cell proliferation was shown to be inhibited by AGEs (Fig. 1B). Finally, treating cells with AGEs (400 µg/ml; 0–4 hours) enhanced migration; however, BSA did not have any effect on migration (Fig. 1C).


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)

Inhibition of cell proliferation by AGEs.SAS cells were treated with AGEs (0–400 µg/ml) or BSA (0–400 µg/ml) for 24 to 48 hours. The number of cells and proliferation were detected using trypan blue dye exclusion (A) and a WST-1 assay (B). AGEs significantly reduced the number of cells; BSA (as a negative control) increased viability (A). AGEs also inhibited cell proliferation (B). Treatment with AGEs (400 µg/ml; 0–4 hours) enhanced cell migration, while treatment with BSA did not (C).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0110542-g001: Inhibition of cell proliferation by AGEs.SAS cells were treated with AGEs (0–400 µg/ml) or BSA (0–400 µg/ml) for 24 to 48 hours. The number of cells and proliferation were detected using trypan blue dye exclusion (A) and a WST-1 assay (B). AGEs significantly reduced the number of cells; BSA (as a negative control) increased viability (A). AGEs also inhibited cell proliferation (B). Treatment with AGEs (400 µg/ml; 0–4 hours) enhanced cell migration, while treatment with BSA did not (C).
Mentions: We first assessed the influence of AGEs on cell viability. SAS cells were treated with AGEs (0–400 µg/ml) or BSA (0–400 µg/ml) for 24 or 48 hours, whereupon the number of cells and proliferation rate were determined according to trypan blue dye exclusion (Fig. 1A) and WST-1 assays (Fig. 1B). Compared with control cells, AGE treated cells showed a significant reduction in number of cells (24 hours AGEs 100: 2.88±0.16, P = 0.006; AGEs 200: 2.6±0.25, P = 0.008; AGEs 400: 1.85±0.05, P <0.0001; 48 hours AGEs 100: 3.1±0.18, P = 0.05; AGEs 200: 2.57±0.17, P = 0.01; AGEs 400: 2.03±0.08, P = 0.003). In contrast, BSA was shown to increase the number of cells (as a negative control, 24 hours: 4.77±0.32, NS; 48 hours: 9.25±0.35, P = 0.0004) (Fig. 1A). In addition, cell proliferation was shown to be inhibited by AGEs (Fig. 1B). Finally, treating cells with AGEs (400 µg/ml; 0–4 hours) enhanced migration; however, BSA did not have any effect on migration (Fig. 1C).

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