title: Establishment and characterization of novel cell lines and xenografts from patients with gastrointestinal stromal tumors.
abstract: At present, no suitable GIST model exists for the analysis of drug resistance or metastasis using established human gastrointestinal stromal tumor (GIST) cell lines or xenografts even though the molecular mechanisms of drug resistance, progression and metastasis require clarification. The aim of this study was to establish and characterize human GIST cell lines and xenografts that can be used for evaluating drug resistance or various new molecularly targeted therapies. GIST tissues from patients were cultured and implanted under the skin of NOG (NOD/Shi-scid, IL-2Rrnu) mice. Two new cell lines (GK1C and GK3C) and three xenografts (GK1X, GK2X and GK3X) were generated from these clinical samples. The established GIST cell lines and xenografts were investigated for tumorigenesis and imatinib sensitivity. These cell lines and xenografts showed characteristic GIST morphology and exhibited KIT expression profiles similar to those of the patient samples. In addition, these GIST cell lines and xenografts were sensitive to imatinib. In conclusion, new human GIST cell lines and xenografts were established and maintained through repeated passages. These models will enable further study of combination therapies and the mechanisms of resistance, and allow testing of novel targeted monotherapies and combination therapies.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sako
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Norihito
authors.initials: N
authors.lastname: Wada
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Kawakubo
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Tai
authors.initials: T
authors.lastname: Ohmori
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate