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https://doi.org/10.1186/s12885-016-2366-2
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 Article breast cancer cell line breast metastasis cell adhesion cell migration cell permeabilization controlled study female human human cell leukocyte mouse nonhuman peripheral blood mononuclear cell pleiotropy protein expression protein function protein phosphorylation tumor growth animal apoptosis Bagg albino mouse breast tumor cell motion cell proliferation disease course drug screening genetics knockout mouse metabolism mononuclear cell pathology physiology secondary tumor cell culture tumor embolism vascular endothelium Animals Antigens, CD44 Apoptosis Breast Neoplasms Cell Adhesion Cell Movement Cell Proliferation Disease Progression E-Selectin Endothelium, Vascular Female Humans Leukocytes, Mononuclear Mice 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. https://doi.org/10.1186/s12885-016-2366-2 | 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 | URI: | https://scholarbank.nus.edu.sg/handle/10635/181366 | ISSN: | 14712407 | DOI: | 10.1186/s12885-016-2366-2 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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