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Title: The effect of soluble E-selectin on tumor progression and metastasis
Authors: Kang, S.-A 
Blache, C.A
Bajana, S
Hasan, N
Kamal, M
Morita, Y
Gupta, V
Tsolmon, B
Suh, S.K
Gorenstein, D.G
Razaq, W
Rui, H
Tanaka, T
Keywords: endothelial leukocyte adhesion molecule 1
CD44 protein, human
endothelial leukocyte adhesion molecule 1
Hermes antigen
animal cell
animal experiment
animal model
breast cancer cell line
breast metastasis
cell adhesion
cell migration
cell permeabilization
controlled study
human cell
peripheral blood mononuclear cell
protein expression
protein function
protein phosphorylation
tumor growth
Bagg albino mouse
breast tumor
cell motion
cell proliferation
disease course
drug screening
knockout mouse
mononuclear cell
tumor cell culture
tumor embolism
vascular endothelium
Antigens, CD44
Breast Neoplasms
Cell Adhesion
Cell Movement
Cell Proliferation
Disease Progression
Endothelium, Vascular
Leukocytes, Mononuclear
Mice, Inbred BALB C
Mice, Knockout
Neoplastic Cells, Circulating
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Issue Date: 2016
Citation: Kang, S.-A, Blache, C.A, Bajana, S, Hasan, N, Kamal, M, Morita, Y, Gupta, V, Tsolmon, B, Suh, S.K, Gorenstein, D.G, Razaq, W, Rui, H, Tanaka, T (2016). The effect of soluble E-selectin on tumor progression and metastasis. BMC Cancer 16 (1) : 331. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: Distant 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. Methods: We investigated the effect of sE-selectin on shear-resistant adhesion and migration of metastatic breast cancer cells and leukocytes in vitro and in vivo. Results: We 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. Conclusions: Our 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. © 2016 The Author(s).
Source Title: BMC Cancer
ISSN: 14712407
DOI: 10.1186/s12885-016-2366-2
Rights: Attribution 4.0 International
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