PMID- 26872904 OWN - NLM STAT- MEDLINE DCOM- 20161114 LR - 20220318 IS - 1573-7217 (Electronic) IS - 0167-6806 (Linking) VI - 155 IP - 3 DP - 2016 Feb TI - High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation. PG - 441-55 LID - 10.1007/s10549-016-3696-0 [doi] AB - Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis. This work indicates a prospective utilization of HDL-based strategies in the treatment of breast cancer patients with type 2 diabetes. FAU - Huang, Xiaoqin AU - Huang X AD - Department of Operating Room, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 40010, China. FAU - He, Dan AU - He D AD - The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. FAU - Ming, Jia AU - Ming J AD - Department of Operating Room, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 40010, China. FAU - He, Yubin AU - He Y AD - The Military General Hospital of Beijing, Beijing, 100700, China. FAU - Zhou, Champion AU - Zhou C AD - The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. FAU - Ren, Hui AU - Ren H AD - Auckland Bioengineering Institute, The University of Auckland, Auckland, 1142, New Zealand. FAU - He, Xin AU - He X AD - Tianjin Key Laboratory of Radiation Medicine and Nuclear Medicine, Institution of Radiation Medicine, Beijing Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Wang, Chenguang AU - Wang C AD - Tianjin Key Laboratory of Radiation Medicine and Nuclear Medicine, Institution of Radiation Medicine, Beijing Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Jin, Jingru AU - Jin J AD - The Military General Hospital of Beijing, Beijing, 100700, China. FAU - Ji, Liang AU - Ji L AD - The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. FAU - Willard, Belinda AU - Willard B AD - Proteomics Core Laboratory, Research Core Services, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. FAU - Pan, Bing AU - Pan B AD - The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. panbintz@163.com. FAU - Zheng, Lemin AU - Zheng L AD - The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. zhengl@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160212 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (E-Selectin) RN - 0 (Lipoproteins, HDL) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Animals MH - Breast Neoplasms/blood/complications/*genetics/pathology MH - Cell Adhesion/*genetics MH - Diabetes Mellitus, Type 2/blood/complications/*genetics/pathology MH - E-Selectin/*biosynthesis/genetics MH - Endothelium, Vascular/pathology MH - Female MH - Gene Expression Regulation, Neoplastic MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Intercellular Adhesion Molecule-1/*biosynthesis MH - Lipoproteins, HDL/blood/genetics MH - MCF-7 Cells MH - Mice MH - Mice, Inbred NOD MH - Neoplasm Metastasis/genetics MH - Neoplastic Cells, Circulating MH - Protein Kinase C/biosynthesis MH - Tumor Necrosis Factor-alpha/biosynthesis MH - Vascular Cell Adhesion Molecule-1/*biosynthesis/genetics OTO - NOTNLM OT - Breast cancer OT - Cell adhesion OT - HDL OT - ICAM-1 OT - Type 2 diabetes mellitus OT - VCAM-1 EDAT- 2016/02/14 06:00 MHDA- 2016/11/15 06:00 CRDT- 2016/02/14 06:00 PHST- 2015/11/10 00:00 [received] PHST- 2016/01/30 00:00 [accepted] PHST- 2016/02/14 06:00 [entrez] PHST- 2016/02/14 06:00 [pubmed] PHST- 2016/11/15 06:00 [medline] AID - 10.1007/s10549-016-3696-0 [pii] AID - 10.1007/s10549-016-3696-0 [doi] PST - ppublish SO - Breast Cancer Res Treat. 2016 Feb;155(3):441-55. doi: 10.1007/s10549-016-3696-0. Epub 2016 Feb 12.