High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells
High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells
复制标题
2型糖尿病患者高密度脂蛋白增强促进乳腺癌细胞迁移和侵袭的能力
DOI：
10.1002/ijc.26341
复制
发表时间：
2012-07-01
影响因子：
6.4
通讯作者：
Zheng, Lemin
中科院分区：
文献类型：
--
作者：
Pan, Bing;Ren, Hui;Zheng, Lemin
流行病学研究表明，2型糖尿病与乳腺癌之间存在复杂的联系。高密度脂蛋白(HDL)与乳腺癌的风险和死亡率之间存在显着的负相关。然而，糖尿病患者的高密度脂蛋白可能会以各种方式改变，这可能会导致对许多不同类型细胞的影响改变。在我们的研究中，我们发现2型糖尿病患者的高密度脂蛋白糖化和氧化水平明显高于健康受试者。糖尿病患者的高密度脂蛋白显著增强了促进细胞增殖、迁移和乳腺癌侵袭的能力(在激素非依赖性细胞和激素依赖性细胞上都进行了检测)。此外，体外产生的糖化和氧化的高密度脂蛋白的作用方式与糖尿病高密度脂蛋白相似。糖尿病高密度脂蛋白、糖化高密度脂蛋白和氧化高密度脂蛋白诱导丙二醛-MB-231细胞合成和分泌更多的血管内皮生长因子-C、基质金属蛋白酶-2和基质金属蛋白酶-9。研究表明，糖尿病、糖化和氧化的高密度脂蛋白通过ERK和p38MAPK途径促进MDA-MB-231细胞的迁移和侵袭，Akt通路在MDA-MB-231细胞侵袭中也起重要作用。Akt、ERK和p38MAPK通路也参与了糖尿病、糖化和氧化高密度脂蛋白诱导的血管内皮生长因子-C和基质金属蛋白酶-9的分泌。我们的研究表明，糖尿病患者高密度脂蛋白的糖基化和氧化可导致对MDA-MB-231细胞的增殖、迁移和侵袭的异常作用，从而促进乳腺癌的进展。这将在很大程度上引起糖尿病患者，特别是乳腺癌患者基于高密度脂蛋白的治疗的注意。
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.