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Title: Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model
Authors: Ding, Laifeng
Zhang, Congcong
Liu, Zhigang
Huang, Qingxia
Zhang, Yinlong
Li, Suping
Nie, Guangjun
Tang, Huiru
Wang, Yulan
Keywords: Science::Medicine
Issue Date: 2020
Source: Ding, L., Zhang, C., Liu, Z., Huang, Q., Zhang, Y., Li, S., . . . Wang, Y. (2019). Metabonomic Investigation of Biological Effects of a New Vessel Target Protein tTF-pHLIP in a Mouse Model. Journal of Proteome Research, 19(1), 238–247. doi:10.1021/acs.jproteome.9b00507
Journal: Journal of Proteome Research
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.
ISSN: 1535-3893
DOI: 10.1021/acs.jproteome.9b00507
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles


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