한빛사 논문
Jong-Jin Kim,†,‡,☆ Yong-An Lee,†,#,☆ Dongdong Su,† Jungyeol Lee,§,∥ Sung-Jin Park,† Beomsue Kim,† Jia Hui Jane Lee,#,∇ Xiao Liu,‡,∥ Seong Soon Kim,⋈ Myung Ae Bae,⋈ Jun-Seok Lee,○ Seong Cheol Hong,○ Lu Wang,†,◆ Animesh Samanta,†,¶ Haw-Young Kwon,‡ So-Young Choi,∥ Jun-Young Kim,□ Young Hyun Yu,▲ Hyung-Ho Ha,▲ Zhenxun Wang,# Wai Leong Tam,#,◊,★ Bing Lim,#,● Nam-Young Kang,*,†,§,⊥ and Young-Tae Chang*,†,‡,∥
† Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
‡ Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 37673, Republic of Korea
§ New Drug Discovery Center, DGMIF, Daegu 41061, Republic of Korea
∥ Department of Chemistry, and ⊥Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea
# Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore 138672, Singapore
∇ School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
○ Molecular Recognition Research Center, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seoul 02792, Republic of Korea
◆ Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg 69120, Germany
¶ Chemical Sciences and Technology Division, CSIR − National Institute for Interdisciplinary Sciences and Technology (CSIR − NIIST), Industrial Estate P O, Pappanamcode, Thiruvananthapuram 695019, India
□ A-fourth, SL VAXiGEN, KOREA BIO PARK, Daewangpangyo-ro 700, Bundang-gu, Seongnam-si, Gyenggi-do 13488, Korea
▲ Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences 11, Sunchon National University, Suncheon 57922, Republic of Korea
◊ Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
★ Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
● Merck Sharp and Dohme Translational Medicine Research Centre, 8A Biomedical Grove, Singapore 138648, Singapore
⋈ Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Gajeong-ro 141, Daejeon 34114, Republic of Korea
*Corresponding Authors
Author Contributions
☆J.-J.K. and Y.-A.L. contributed equally.
Abstract
Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment.
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