期刊论文详细信息
BMC Cancer | |
The effect of soluble E-selectin on tumor progression and metastasis | |
Research Article | |
Wajeeha Razaq1  Hallgeir Rui2  Yoshihiro Morita3  Shin-Ae Kang3  Mohamed Kamal3  Vineet Gupta3  Bilegtsaikhan Tsolmon3  Sandra Bajana3  Takemi Tanaka4  David G. Gorenstein5  K. Stephen Suh6  Celine A. Blache7  Nafis Hasan7  | |
[1]Department of Internal Medcine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th, 73104, Oklahoma City, OK, USA | |
[2]Department of Pathology, Medical College of Wisconsin Cancer Center, 8701 Watertown Plank Rd, 53226, Milwaukee, WI, USA | |
[3]Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE, 10th, 73104, Oklahoma City, OK, USA | |
[4]Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE, 10th, 73104, Oklahoma City, OK, USA | |
[5]Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, 975 NE 10th, 73104, Oklahoma City, OK, USA | |
[6]Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, 77030, Houston, TX, USA | |
[7]John Theurer Cancer Center, Hackensack University Medical Center, 07601, Hackensack, NJ, USA | |
[8]Thomas Jefferson University, Pharmaceutical Sciences, 1020 Locust St, 19107, Philadelphia, PA, USA | |
关键词: sE-selectin; E-selectin; Shear-resistant adhesion; CD44; Hematogenous metastasis; | |
DOI : 10.1186/s12885-016-2366-2 | |
received in 2015-12-21, accepted in 2016-05-17, 发布年份 2016 | |
来源: Springer | |
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【 摘 要 】
BackgroundDistant metastasis resulting from vascular dissemination of cancer cells is the primary cause of mortality from breast cancer. We have previously reported that E-selectin expression on the endothelial cell surface mediates shear-resistant adhesion and migration of circulating cancer cells via interaction with CD44. As a result of shedding, soluble E-selectin (sE-selectin) from the activated endothelium is present in the serum. In this study, we aimed to understand the role of sE-selectin in tumor progression and metastasis.MethodsWe investigated the effect of sE-selectin on shear-resistant adhesion and migration of metastatic breast cancer cells and leukocytes in vitro and in vivo.ResultsWe found that sE-selectin promoted migration and shear-resistant adhesion of CD44+/high breast cancer cell lines (MDA-MB-231 and MDA-MB-468) to non-activated human microvessel endothelial cells (ES-HMVECs), but not of CD44-/low breast cancer cell lines (MCF-7 and T-47D). This endothelial E-selectin independent, sE-selectin-mediated shear-resistant adhesion was also observed in a leukocyte cell line (HL-60) as well as human peripheral blood mononuclear cells (PBMCs). Additionally, the incubation of MDA-MB-231 cells with sE-selectin triggered FAK phosphorylation and shear-resistant adhesion of sE-selectin-treated cells resulted in increased endothelial permeabilization. However, CD44 knockdown in MDA-MB-231 and HL-60 cells resulted in a significant reduction of sE-selectin-mediated shear-resistant adhesion to non-activated HMVECs, suggesting the involvement of CD44/FAK. Moreover, functional blockade of ICAM-1 in non-activated HMVECs resulted in a marked reduction of sE-selectin-mediated shear-resistant adhesion. Finally, the pre-incubation of CD44+ 4 T1 murine breast cancer cells with sE-selectin augmented infiltration into the lung in E-selectin K/O mice and infusion of human PBMCs pre-incubated with sE-selectin stimulated MDA-MB-231 xenografted breast tumor growth in NSG mice.ConclusionsOur data suggest that circulating sE-selectin stimulates a broad range of circulating cells via CD44 and mediates pleiotropic effects that promote migration and shear-resistant adhesion in an endothelial E-selectin independent fashion, in turn accelerating tissue infiltration of leukocytes and cancer cells.【 授权许可】
CC BY
© The Author(s). 2016
【 预 览 】
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