Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen.
Cancer cells secrete small membranous extracellular vesicles (EVs) into their microenvironment and circulation. Although their potential as cancer biomarkers has been promising, the identification and quantification of EVs in clinical samples remains challenging. Here we describe a sensitive and rapid analytical technique for profiling circulating EVs directly from blood samples of patients with colorectal cancer. EVs are captured by two types of antibodies and are detected by photosensitizer-beads, which enables us to detect cancer-derived EVs without a purification step. We also show that circulating EVs can be used for detection of colorectal cancer using the antigen CD147, which is embedded in cancer-linked EVs. This work describes a new liquid biopsy technique to sensitively detect disease-specific circulating EVs and provides perspectives in translational medicine from the standpoint of diagnosis and therapy.
1] Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan [2] Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo 162-8480, Japan [3] Research Fellow of the Japan Society for the Promotion of Science (JSPS), Chiyoda-Ku, Tokyo 102-0083, Japan.
Yusuke
Y
Yoshioka
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Nobuyoshi
N
Kosaka
1] Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan [2] R&D Department, SRL Inc., Hino-shi, Tokyo 191-0002, Japan.
Yuki
Y
Konishi
Diagnostics Division, Shionogi & Co., LTD., Settsu-shi, Osaka 566-0022, Japan.
Hideki
H
Ohta
Diagnostics Division, Shionogi & Co., LTD., Settsu-shi, Osaka 566-0022, Japan.
Hiroyuki
H
Okamoto
Diagnostics Division, Shionogi & Co., LTD., Settsu-shi, Osaka 566-0022, Japan.
Hikaru
H
Sonoda
Department of Gastroenterological Surgery, Graduated School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Ryoji
R
Nonaka
Department of Gastroenterological Surgery, Graduated School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Hirofumi
H
Yamamoto
Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Hideshi
H
Ishii
Department of Gastroenterological Surgery, Graduated School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Masaki
M
Mori
Division of Clinical Laboratories, National Cancer Center Hospital, Chuo-ku Tokyo, 104-0045, Japan.
Koh
K
Furuta
Endoscopy Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Takeshi
T
Nakajima
R&D Department, SRL Inc., Hino-shi, Tokyo 191-0002, Japan.
Hiroshi
H
Hayashi
R&D Department, SRL Inc., Hino-shi, Tokyo 191-0002, Japan.
Hajime
H
Sugisaki
R&D Department, SRL Inc., Hino-shi, Tokyo 191-0002, Japan.
Hiroko
H
Higashimoto
Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo 162-8480, Japan.
Takashi
T
Kato
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Fumitaka
F
Takeshita
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Takahiro
T
Ochiya
D051926:Basigin / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005110:Extracellular Space; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D022142:Secretory Vesicles / Q000378:metabolism*; D060225:Tetraspanin 28 / Q000378:metabolism; D060245:Tetraspanin 29 / Q000378:metabolism; D060149:Tetraspanin 30 / Q000378:metabolism
C497886:BSG protein, human; D014408:Biomarkers, Tumor; C554586:CD63 protein, human; C554798:CD81 protein, human; C554869:CD9 protein, human; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; D051926:Basigin