Metabonomic Investigation of Biological Effects of a New Vessel Target Protein tTF-pHLIP in a Mouse Model

Laifeng Ding, Congcong Zhang, Zhigang Liu, Qingxia Huang, Yinlong Zhang, Suping Li, Guangjun Nie, Huiru Tang, Yulan Wang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In recent years, tumor microenvironment (TME) has been recognized as potential targets for tumor treatment and the tumor vascular system is one of such targets. Fusing truncated tissue factor (tTF) with pH low insertion peptides (pHLIP), tTF-pHLIP, can target tumor vessels owing to its acidic TME and cause tumor vessel occlusion by blood clotting and subsequently effectively inhibit tumor growth. To evaluate its bioeffects, we exposed the tTF-pHLIP to normal mice and mice xenograft with B16F10 tumor and analyzed the metabolic profiling of various tissues and biofluids including plasma and urine from mice treated with and without tTF-pHLIP. A combination of nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry and ultra-high-performance liquid chromatography-mass spectrometry was employed in the study. We found that tTF-pHLIP treatment can effectively reduce tumor size and concurrently ameliorate tumor-induced alterations in the TCA cycle metabolism and lipid metabolism. In addition, we found that toxicity of tTF-pHLIP to normal mice is minor and exposure of the tTF-pHLIP induced oxidative stress to the system. Hence, we concluded that tTF-pHLIP is of low toxicity and effective in reducing tumor size as well as rebalancing tumor-induced metabolic derailment.

Original languageEnglish (US)
Pages (from-to)238-247
Number of pages10
JournalJournal of Proteome Research
Volume19
Issue number1
DOIs
StatePublished - Jan 3 2020

Keywords

  • biological effects
  • melanoma
  • metabonomics
  • vessel target protein

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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