Kawamoto, Eiji and Nago, Nodoka and Okamoto, Takayuki and Gaowa, Arong and Masui-Ito, Asami and Akama, Yuichi and Darkwah, Samuel and Appiah, Michael Gyasi and Myint, Phyoe Kyawe and Obeng, Gideon and Ito, Atsushi and Caidengbate, Siqingaowa and Esumi, Ryo and Yamaguchi, Takanori and Park, Eun Jeong and Imai, Hiroshi and Shimaoka, Motomu (2021) The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin. Biomedicines, 9 (2). p. 162. ISSN 2227-9059
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Abstract
Thrombomodulin is a molecule with anti-coagulant and anti-inflammatory properties. Recently, thrombomodulin was reported to be able to bind extracellular matrix proteins, such as fibronectin and collagen; however, whether thrombomodulin regulates the binding of human breast cancer-derived cell lines to the extracellular matrix remains unknown. To investigate this, we created an extracellular domain of thrombomodulin, TMD123-Fc, or domain deletion TM-Fc proteins (TM domain 12-Fc, TM domain 23-Fc) and examined their bindings to fibronectin in vitro by ELISA. The lectin-like domain of thrombomodulin was found to be essential for the binding of the extracellular domain of thrombomodulin to fibronectin. Using a V-well cell adhesion assay or flow cytometry analysis with fluorescent beads, we found that both TMD123-Fc and TMD12-Fc inhibited the binding between β1 integrin of human breast cancer-derived cell lines and fibronectin. Furthermore, TMD123-Fc and TMD12-Fc inhibited the binding of activated integrins to fibronectin under shear stress in the presence of Ca2+ and Mg2+ but not under strong integrin-activation conditions in the presence of Mg2+ without Ca2+. This suggests that thrombomodulin Fc fusion protein administered exogenously at a relatively early stage of inflammation may be applied to the development of new therapies that inhibit the binding of β1 integrin of breast cancer cell lines to fibronectin.
Item Type: | Article |
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Subjects: | Universal Eprints > Biological Science |
Depositing User: | Managing Editor |
Date Deposited: | 13 Mar 2023 05:01 |
Last Modified: | 23 May 2024 05:16 |
URI: | http://journal.article2publish.com/id/eprint/1050 |