Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model
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 an...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/144048 |
| _version_ | 1826124448440254464 |
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| author | Ding, Laifeng Zhang, Congcong Liu, Zhigang Huang, Qingxia Zhang, Yinlong Li, Suping Nie, Guangjun Tang, Huiru Wang, Yulan |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Ding, Laifeng Zhang, Congcong Liu, Zhigang Huang, Qingxia Zhang, Yinlong Li, Suping Nie, Guangjun Tang, Huiru Wang, Yulan |
| author_sort | Ding, Laifeng |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T06:20:30Z |
| format | Journal Article |
| id | ntu-10356/144048 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:20:30Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1440482020-11-01T05:23:25Z Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model Ding, Laifeng Zhang, Congcong Liu, Zhigang Huang, Qingxia Zhang, Yinlong Li, Suping Nie, Guangjun Tang, Huiru Wang, Yulan Lee Kong Chian School of Medicine (LKCMedicine) Singapore Phenome Center Science::Medicine Vessel Target Protein Biological Effects 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. Accepted version 2020-10-09T07:28:51Z 2020-10-09T07:28:51Z 2020 Journal Article 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 1535-3893 https://hdl.handle.net/10356/144048 10.1021/acs.jproteome.9b00507 31603327 1 19 238 247 en Journal of Proteome Research 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 https://doi.org/10.1021/acs.jproteome.9b00507 application/pdf |
| spellingShingle | Science::Medicine Vessel Target Protein Biological Effects Ding, Laifeng Zhang, Congcong Liu, Zhigang Huang, Qingxia Zhang, Yinlong Li, Suping Nie, Guangjun Tang, Huiru Wang, Yulan Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model |
| title | Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model |
| title_full | Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model |
| title_fullStr | Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model |
| title_full_unstemmed | Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model |
| title_short | Metabonomic investigation of biological effects of a new vessel target protein tTF-pHLIP in a mouse model |
| title_sort | metabonomic investigation of biological effects of a new vessel target protein ttf phlip in a mouse model |
| topic | Science::Medicine Vessel Target Protein Biological Effects |
| url | https://hdl.handle.net/10356/144048 |
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