Studying the role of thrombomodulin-plasminogen interaction in spatial and interfacial invasion of melanoma metastatic progression

Int J Biol Macromol. 2025 Jan;284(Pt 1):138053. doi: 10.1016/j.ijbiomac.2024.138053. Epub 2024 Nov 24.

Abstract

Thrombomodulin (TM), a transmembrane glycoprotein, has emerged as a key factor in the metastatic spread of various cancers, including malignant melanoma. Despite its recognized significance, the underlying mechanisms of TM's involvement in enhancing metastasis remain incompletely understood. This study addresses this knowledge gap by utilizing spatial and interfacial invasion models in vitro to investigate the effect of the interaction between TM and plasminogen (Plg) on melanoma invasion. While it is well established that Plg induces a chain reaction in the plasmin system, leading to the activation of metalloproteases that promote tumor cell invasion and metastasis, this study is the first to demonstrate that TM binding to Plg can enhance these activations in spatial and interfacial invasion models in vitro. These results highlight the potential of TM as a crucial target for the development of drugs aimed at significantly inhibiting melanoma metastasis and improving patient survival.

Keywords: Interfacial invasion; Melanoma spheroid; Plasminogen; Spatial invasion; Thrombomodulin.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression
  • Humans
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis
  • Plasminogen* / metabolism
  • Protein Binding
  • Thrombomodulin* / metabolism

Substances

  • Thrombomodulin
  • Plasminogen