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 | Kazumasa Fukuda, Yoshiro Saikawa, Hiroyuki Sako, Yumi Yoshimura, Tsunehiro Takahashi, Norihito Wada, Hirohumi Kawakubo, Hiroya Takeuchi, Tai Ohmori, Yuko Kitagawa |
Journal | Oncology reports
(Oncol Rep)
Vol. 30
Issue 1
Pg. 71-8
(Jul 2013)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 23619463
(Publication Type: Journal Article)
|
Chemical References |
- Antineoplastic Agents
- Benzamides
- Piperazines
- Pyrimidines
- Imatinib Mesylate
|
Topics |
- Adult
- Aged
- Animals
- Antineoplastic Agents
(pharmacology)
- Benzamides
(pharmacology)
- Carcinogenesis
- Cell Line, Tumor
- Drug Resistance, Neoplasm
- Female
- Gastrointestinal Stromal Tumors
(drug therapy, metabolism)
- Heterografts
- Humans
- Imatinib Mesylate
- Male
- Mice
- Mice, Inbred NOD
- Middle Aged
- Molecular Targeted Therapy
- Neoplasm Transplantation
- Piperazines
(pharmacology)
- Pyrimidines
(pharmacology)
- Transplantation, Heterologous
|