title: Colorectal cancer-derived tumor spheroids retain the characteristics of original tumors.
abstract: Primary cultures of cancer cells are useful for developing personalized medicine. In this study, we characterized three lines of three-dimensional (3D) tumor spheroids established directly from tumor tissues of patients with colorectal cancers (CRCs). Each line mainly included EpCAM-positive cells and cells expressing putative cancer stem cell markers such as CD133, CD44, CD24, ALDH1, and LGR5. These characteristic stem cell markers remained identically for months in vitro. Short tandem repeat genotyping suggested that genetic fingerprints of these tumor spheroids were similar to those of the original tumor tissues from which they were derived. Mutational analysis showed that each line had the same mutation profile for APC, KRAS, MLH1, serine-threonine kinase 11, and TP53 as its parental tumor tissue. One line harboring an activating KRAS mutation was resistant to cetuximab while the remaining two lines harboring wild-type KRAS showed different responses to cetuximab. Immunohistochemical analysis showed that xenograft tumors derived from these lines retained the histopathological and mutational patterns of their parental tumors. Collectively, these results clearly showed that 3D tumor spheroids directly generated from tumor tissues of patients with CRCs preserved the characteristics of their parental tumor tissues and could be used for developing personalized medicines for CRCs.
authors.affiliation: New Drug Development Center, Daegu-Gyungbuk Medical Innovation Foundation, Daegu, Republic of Korea.
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Medical Center, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jun Hwa
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Hwan Ki
authors.initials: HK
authors.lastname: Park
authors.affiliation: Colorectal Cancer Center, Kyungpook National University Medical Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jun Seok
authors.initials: JS
authors.lastname: Park
authors.affiliation: Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Bo-Kyung
authors.initials: BK
authors.lastname: Kim
authors.affiliation: Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Jung-Yi
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Ghil Suk
authors.initials: GS
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Colorectal Cancer Center, Kyungpook National University Medical Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: kyuschoi@mail.knu.ac.kr.
authors.forename: Gyu-Seog
authors.initials: GS
authors.lastname: Choi
authors.affiliation: Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Medical Center, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: leei@knu.ac.kr.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D056910:Republic of Korea; D018874:Spheroids, Cellular; D013997:Time Factors; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D000068818:Cetuximab
keywords: Colorectal cancer; Spheroid cultures; Xenograft