Cell Migration Is Regulated by AGE-RAGE Interaction in Human Oral Cancer Cells In Vitro

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 b...

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Published in:PloS one Vol. 9; no. 10; p. e110542
Main Authors: Ko, Shun-Yao, Ko, Hshin-An, Shieh, Tzong-Ming, Chang, Weng-Cheng, Chen, Hong-I, Chang, Shu-Shing, Lin, I-Hsuan
Format: Journal Article
Language:English
Published: United States Public Library of Science 16.10.2014
Public Library of Science (PLoS)
Subjects:
Adult
Advanced glycosylation end products
Age
Alzheimer's disease
Angiogenesis
Biology and Life Sciences
Cancer
Carbohydrates
Cell adhesion & migration
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell Proliferation - drug effects
Cell Proliferation - genetics
Complications
Correlation analysis
Diabetes
Diabetes Complications - genetics
Diabetes Complications - pathology
Diabetes mellitus
Diabetes Mellitus - genetics
Diabetes Mellitus - pathology
Diabetics
Enzymes
Experiments
Female
Flavonoids - administration & dosage
Fluorides
Gelatinase A
Gelatinase B
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Glycation End Products, Advanced - genetics
Glyceraldehyde
Glycosylation
Health risks
Humans
Male
Malignancy
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 9 - biosynthesis
Medicine
Melanoma
Metastases
Metastasis
Mouth cancer
Mouth Neoplasms - complications
Mouth Neoplasms - genetics
Mouth Neoplasms - pathology
Neoplasm Metastasis
Oral cancer
Patients
Penicillin
Phosphorylation
Proteins
Receptor for Advanced Glycation End Products - antagonists & inhibitors
Receptor for Advanced Glycation End Products - genetics
Risk factors
RNA, Small Interfering
RNA-mediated interference
Science
Survival
United States > US
Taiwan
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: SYK. Performed the experiments: HAK SSC IHL. Analyzed the data: SYK HAK. Contributed reagents/materials/analysis tools: SYK TMS WCC HIC. Wrote the paper: SYK.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0110542