Thrombomodulin-mediated cell adhesion: Involvement of its lectin-like domain

Huey Chun Huang, Guey Yueh Shi, Shinn Jong Jiang, Chung Sheng Shi, Chun Mei Wu, Hsi Yuan Yang, Hua Lin Wu

研究成果: Article同行評審

131 引文 斯高帕斯(Scopus)

摘要

Thrombomodulin (TM) is an integral membrane glycoprotein that is a potent anticoagulant factor. TM may also possess functions distinct from its anticoagulant activity. Here the influence of TM on cell adhesion was studied in TM-negative melanoma A2058 cells transfected with green fluorescent protein-tagged TM (TMG) or lectin domain-deleted TM (TMG(ΔL)). Confocal microscopy demonstrated that both TMG and TMG(ΔL) were distributed in the plasma membrane. TMG-expressed cells grew as closely clustered colonies, with TM localized prominently in the intercellular boundaries. TMG(Δ L)-expressed cells grew singly. Overexpression of TMG, but not TMG(ΔL), decreased monolayer permeability in vitro and tumor growth in vivo. The cell-to-cell adhesion in TMG-expressed cells was Ca2+-dependent and was inhibited by monoclonal antibody against the lectin-like domain of TM. The effects of TM-mediated cell adhesion were abolished by the addition of mannose, chondroitin sulfate A, or chondroitin sulfate C. In addition, anti-lectin-like domain antibody disrupted the close clustering of the endogenous TM-expressed keratinocyte HaCaT cell line derived from normal human epidermis. Double-labeling immunofluorescence staining revealed similar distributions of TM and actin filament in the cortex region of the TMG-expressed cells. Thus, TM can function as a Ca2+-dependent cell-to-cell adhesion molecule. Binding of specific carbohydrates to the lectin-like domain is essential for this specific function.

原文English
頁(從 - 到)46750-46759
頁數10
期刊Journal of Biological Chemistry
278
發行號47
DOIs
出版狀態Published - 2003 十一月 21

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 細胞生物學

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