Specific tissue factor delivery using a tumor-homing peptide for inducing tumor infarction

Quanwei Shi, Yinlong Zhang, Shaoli Liu, Guangna Liu, Junchao Xu, Xiao Zhao, Gregory J. Anderson, Guangjun Nie, Suping Li

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Targeting the human blood coagulation-inducing protein tissue factor (TF) to the tumor vasculature to induce infarction and disrupt the blood vessels has proven to be an effective approach for tumor therapy. In this study, we investigated the thrombogenic activity and anti-tumor potential of a novel fusion protein (tTF-CREKA) comprising the extracellular domain of human tissue factor (truncated TF, tTF) and a tumor targeting pentapeptide, Cys-Arg-Glu-Lys-Ala (CREKA). tTF is soluble and inactive in its free state, but when it is targeted to the plasma membrane of both tumor vessel endothelial cells and stromal cells by the CREKA peptide, its native coagulation-inducing activity is restored. Systemic administration of the tTF-CREKA fusion protein into tumor-bearing mice induced tumor-selective intravascular thrombosis and reduced tumor blood perfusion, consequently inhibiting tumor growth. The development of tTF-CREKA introduces a new method for treating a wide spectrum of solid tumors by selectively blocking tumor blood supply.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalBiochemical pharmacology
Volume156
DOIs
StatePublished - Oct 2018

Keywords

  • CREKA
  • Thrombosis
  • Tumor inhibition
  • Tumor vessels
  • tTF-fusion proteins

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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