title: High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells.
abstract: Epidemiological studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. There is a significant inverse association between high-density lipoprotein (HDL) and the risk and mortality of breast cancer. However, HDL could be modified in various ways in diabetes patients, and this may lead to the altered effects on many different types of cells. In our study, we found that glycation and oxidation levels are significantly higher in HDL from type 2 diabetes mellitus patients compared to that from healthy subjects. Diabetic HDL dramatically had a stronger capability to promote cell proliferation, migration and invasion of breast cancer (as examined both on hormone-independent cells and on hormone-dependent cells). In addition, glycated and oxidized HDL, which were produced in vitro, acted in similar way as diabetic HDL. Diabetic HDL, glycated HDL and oxidized HDL also induced higher synthesis and secretion of VEGF-C, MMP-2 and MMP-9 from malondialdehyde (MDA)-MB-231 cells. It was indicated that diabetic, glycated and oxidized HDL promote MDA-MB-231 cell migration and invasion through ERK and p38 MAPK pathways, and Akt pathway plays an important role as well in MDA-MB-231 cell invasion. The Akt, ERK and p38 MAPK pathways are also involved in VEGF-C and MMP-9 secretion induced by diabetic, glycated and oxidized HDL. Our study demonstrated that glycation and oxidation of HDL in diabetic patients could lead to abnormal actions on MDA-MB-231 cell proliferation, migration and invasion, thereby promoting the progression of breast cancer. This will largely draw the attention of HDL-based treatments in diabetic patients especially those with breast cancer.
authors.affiliation: The Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Haidian District, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: Yijing
authors.initials: Y
authors.lastname: Ma
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.forename: Baoqi
authors.initials: B
authors.lastname: Yu
authors.forename: Liang
authors.initials: L
authors.lastname: Ji
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Liangui
authors.initials: L
authors.lastname: Yang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lv
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Shen
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.forename: Yubin
authors.initials: Y
authors.lastname: He
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010084:Oxidation-Reduction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008075:Lipoproteins, HDL; D042582:Vascular Endothelial Growth Factor C; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9