Advanced glycation endproducts increase proliferation, migration and invasion of the breast cancer cell line MDA-MB-231

Abstract

Diabetic patients have increased likelihood of developing breast cancer. Advanced glycation endproducts (AGEs) underlie the pathogenesis of diabetic complications but their impact on breast cancer cells is not understood. This study aims to determine the effects of methylglyoxal-derived bovine serum albumin AGEs (MG-BSA-AGEs) on the invasive MDA-MB-231 breast cancer cell line. By performing cell counting, using wound-healing assay, invasion assay and zymography analysis, we found that MG-BSA-AGEs increased MDA-MB-231 cell proliferation, migration and invasion through Matrigel™ associated with an enhancement of matrix metalloproteinase (MMP)-9 activities, in a dose-dependent manner. Using Western blot and flow cytometry analyses, we demonstrated that MG-BSA-AGEs increased expression of the receptor for AGEs (RAGE) and phosphorylation of key signaling protein extracellular signal-regulated kinase (ERK)-1/2. Furthermore, in MG-BSA-AGE-treated cells, phospho-protein micro-array analysis revealed enhancement of phosphorylation of the ribosomal protein 70 serine S6 kinase beta 1 (p70S6K1), which is known to be involved in protein synthesis, the signal transducer and activator of transcription (STAT)-3 and the mitogen-activated protein kinase (MAPK) p38, which are involved in cell survival. Blockade of MG-BSA-AGE/RAGE interactions using a neutralizing anti-RAGE antibody inhibited MG-BSA-AGE-induced MDA-MB-231 cell processes, including the activation of signaling pathways. Throughout the study, non-modified BSA had a negligible effect. In conclusion, AGEs might contribute to breast cancer development and progression partially through the regulation of MMP-9 activity and RAGE signal activation. The up-regulation of RAGE and the concomitant increased phosphorylation of p70S6K1 induced by AGEs may represent promising targets for drug therapy to treat diabetic patients with breast cancer.

RETRACTED: Advanced Glycation End-Products Enhance Lung Cancer Cell Invasion and Migration

“…These findings suggest that these two AGEs might benefit NSCLC metastasis. Sharaf et al [7] and Ko et al [17] reported that AGEs enhanced proliferation, invasion and migration in oral and breast cancer cells. The study of Takino et al [14] revealed that glyceraldehyde-derived AGEs at 20–100 μg/mL increased the migration capacity of A549 cells.…”

“…So far, the impact of endogenous or exogenous AGEs upon cancer progression has been a focus because AGE levels were found to be markedly elevated in both serum and tumors, especially in more aggressive tumors [5]. Kim et al [6] and Sharaf et al [7] indicated that the engagement of AGEs with their receptor (RAGE) further up-regulated RAGE protein expression, and subsequently activated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways in myeloid leukemia and breast cancer cells.…”

Advanced Glycation End-Products: A Biological Consequence of Lifestyle Contributing to Cancer Disparity

“…AGE presence in human tumors was first demonstrated in larynx, breast and colon tumors by immune-histochemical staining. Exogenous AGE treatment of breast (7) and prostate (8) immortalized cancer cell lines promotes cell growth, migration and invasion. In prostate cancer, AGE modified basement membrane promotes the invasive properties of prostate epithelial cells and correlates with decreased survival (8).…”

Maillard Reactions – An Important Factor of the Safety and Quality of Infant Formula

“…Избыточная экспрессия рецепторов RAGE и VEGF-A в тканях глаза (на приме-ре лабораторных животных, получавших корм с высоким содержанием ПРМ); воспаление и паталогическая неоваскуляризация в структурах глаз; дегенерация макулы; образование катаракты, диабетическая ретинопатия, глаукома [32][33] Новообразования Влияние на миграцию и инвазию опухолевых клеток; накопление ПРМ в боль-шем количестве в злокачественных новообразованиях, чем доброкачественных [34][35][36] …”