Oncotarget

Research Papers:

MR molecular imaging of tumors based on an optimal hTERT promoter tyrosinase expression system

Chuan Li, Chang-Jiang Hu, Bo Tang, Xin Yong, Gang Luo, Yu-Yun Wu, Su-Min Wang, Song-Tao Yu and Shi-Ming Yang _

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Oncotarget. 2016; 7:42474-42484. https://doi.org/10.18632/oncotarget.9888

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Abstract

Chuan Li1,2,*, Chang-Jiang Hu2,*, Bo Tang2, Xin Yong2, Gang Luo2, Yu-Yun Wu2, Su-Min Wang2, Song-Tao Yu2,3, Shi-Ming Yang2

1Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China

2Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China

3Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Shi-Ming Yang, email: shimingyang@yahoo.com

Keywords: MR molecular imaging, hTERT promoter, tyrosinase, melanin

Abbreviations: hTERT=human telomerase reverse transcriptase, CT=computed tomography, MRI= magnetic resonance imaging, TYR=tyrosinase

Received: October 08, 2015     Accepted: May 13, 2016     Published: June 7, 2016

ABSTRACT

The early diagnosis and treatment of tumors is of vital significance to increase patient survival. Therefore, we constructed a lentiviral vector expressing tyrosinase (TYR) driven by an optimized human telomerase reverse transcriptase (hTERT) promoter or a cytomegalovirus(CMV) promoter in the hopes of performing noninvasive and real-time tumor-specific imaging. First, hTERT-TYR and CMV-TYR were constructed to infect cancer cell lines (telomerase-negative cell line: U2OS; telomerase-positive cell lines: SGC-7901, SW480 and HepG2). Subsequently, stable tyrosinase-expressing cell lines were sorted by flow cytometry out of these infected cancer cell lines. Then, the mRNA and protein levels of tyrosinase were analyzed. Thetyrosinase activity, melanin production and ferric ion adsorption were measured followed by an MR scan. Consequently the results showed that tyrosinase was only expressed in telomerase-positive tumor cells infected by hTERT-TYR, whereas tyrosinase was expressed in both telomerase-negative and telomerase-positive tumor cells infected by CMV-TYR. Finally, we performed in vivo tumor MR using a clinical 3T MR scanner and found increased signals at T1W1 from telomerase-positive cells infected by hTERT-TYR, which revealed that MR scanning could distinguish cells with hTERT -positive cells from hTERT-negative cells infected with the optimized lentivirus. The mechanism underlying this effect is that tyrosinase promotes melanin production and ferric ion adsorption only in hTERT-expressing cells. Taken together, these data show that this optimized hTERT promoter-driving tyrosinase expression system might be a useful diagnostic tool for the detection of tumors using MR imaging.


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