RETRACTED: 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 hormonedependent 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.Breast cancer is the most common malignant neoplasm in females, with more than 1.15 million new cases occurring worldwide annually, 1 and is one of the leading causes of cancer-related death. 2 Meanwhile, diabetes mellitus has an estimated prevalence of 220 million people worldwide. It is estimated that about 95% of adults with diabetes have type 2

Oxidized High-Density Lipoprotein Induces the Proliferation and Migration of Vascular Smooth Muscle Cells by Promoting the Production of ROS

“…The proproliferative and promigratory effects of ox-HDL were found to be positively correlated with intracellular NADPH oxidase activation and ROS production. enhances the proliferation, migration and invasion of breast cancer cells, while hypochlorite-induced oxidative stress elevates the capability of HDL to promote breast cancer metastasis, which demonstrates that ox-HDL and oxidative stress play essential roles in the proliferation and migration of cells 28,29) . In this study, our results showed that compared with N-HDL, ox-HDL significantly promoted the proliferation of VSMCs in a dose-dependent manner (Fig.…”

“…Under the state of chronic inflammation observed in atherosclerosis, the VSMC phenotype shifts from a quiescent contractile state to an active synthetic state. Synthetic phenotypes of VSMCs proliferate and migrate from the medial layer of the vessel migration and invasion of breast cancer cells, thereby promoting the progression of breast cancer 28) . Furthermore, hypochlorite-induced oxidative stress elevates the ability of HDL to promote breast cancer metastasis 29) .…”

Impact of body mass on recurrence and progression in Chinese patients with Ta, T1 urothelial bladder cancer

“…Indirectly, hyperglycemia increases levels of insulin, insulin-like growth factor-1 and inflammatory cytokines, all of which constitute the microenvironment facilitating the tumor growth [21]. Glycation and oxidation of high-density lipoprotein in diabetic patients would also lead to active tumor cells [22]. Besides, high glucose impairs effective phagocytosis and mitosis of lymphocytes, thus decreasing immune surveillance [23].…”

Correlations of microRNA-124a and microRNA-30d with clinicopathological features of breast cancer patients with type 2 diabetes mellitus

“…It is reported that approximately 7% of the people worldwide in the age between 20 and 79 years is estimated to have DM in 2010 and the number is expected to rise by more than 50% in the next 20 years (Ginter and Simko 2012). Further, studies focused on the DM have demonstrated that DM was implicated in various cancers development, including pancreas cancer, colon cancer, liver cancer, esophagus cancer, endometrial cancer and BC (Chang et al 2012; Pan et al 2012; Shikata et al 2013; Wang et al 2012). The relative risk for mortality of BC patients has been reported to be twofold greater in BC patients with DM than in those without DM (Liao et al 2011), and the epidemiologic evidences showed that DM patients have a significant higher risk of BC and is closely associated with a poor prognosis of BC patients (Luo et al 2014; Oppong et al 2014).…”