Nejvíce citovaný článek - PubMed ID 11206839
The chick-embryo model has been an important tool to study tumor growth, metastasis, and angiogenesis. However, an imageable model with a genetic fluorescent tag in the growing and spreading cancer cells that is stable over time has not been developed. We report here the development of such an imageable fluorescent chick-embryo metastatic cancer model with the use of green fluorescent protein (GFP). Lewis lung carcinoma cells, stably expressing GFP, were injected on the 12th day of incubation in the chick embryo. GFP-Lewis lung carcinoma metastases were visualized by fluorescence, after seven days additional incubation, in the brain, heart, and sternum of the developing chick embryo, with the most frequent site being the brain. The combination of streptokinase and gemcitabine was evaluated in this GFP metastatic model. Twelve-day-old chick embryos were injected intravenously with GFP-Lewis lung cancer cells, along with these two agents either alone or in combination. The streptokinase-gemcitabine combination inhibited metastases at all sites. The effective dose of gemcitabine was found to be 10 mg/kg and streptokinase 2000 IU per embryo. The data in this report suggest that this new stably fluorescent imageable metastatic-cancer chick-embryo model will enable rapid screening of new antimetastatic agents.
- MeSH
- deoxycytidin aplikace a dávkování analogy a deriváty MeSH
- gemcitabin MeSH
- karcinom plic Lewisové farmakoterapie MeSH
- kuřecí embryo MeSH
- léky antitumorózní - screeningové testy metody MeSH
- metastázy nádorů prevence a kontrola MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- streptokinasa aplikace a dávkování MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Názvy látek
- deoxycytidin MeSH
- gemcitabin MeSH
- streptokinasa MeSH
- zelené fluorescenční proteiny MeSH
The Lewis lung tumor has been extensively studied in both syngeneic and allogeneic mouse models. However, its metastatic potential and mechanism are poorly understood. The aim of the present study was to develop a highly metastatic lymph-node targeting, imageable model of the Lewis lung carcinoma in a syngeneic host. We report here a syngeneic model of the Lewis lung carcinoma in which the carcinoma cells are labeled with green fluorescent protein (GFP). The tumor cells were transplanted in the dorsal side of the ear of C57-B16 mice in order to give the tumor cells access to the lymphatic system. This model of the Lewis lung carcinoma extensively metastasized to numerous lymph nodes throughout the body of the animal as well as visceral organs, as visualized by fluorescence microscopy using the bright GFP signal. Twenty-one different metastatic sites, including lymph nodes throughout the body, were identified among the cohort of transplanted animals. The data demonstrate a predilection of the Lewis lung carcinoma for lymphatic pathways for metastasis throughout the animal body. The concomitant macrometastases to the visceral organs observed in this model may be remetastasis from the lymph nodes. This model of the Lewis lung carcinoma should be very useful in defining cellular trafficking and targeting mechanisms of metastasis, in particular those involving lymphatic pathways.
- MeSH
- fluorescenční mikroskopie MeSH
- karcinom plic Lewisové sekundární MeSH
- luminescentní proteiny * MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny patologie MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Retroviridae genetika MeSH
- transplantace nádorů MeSH
- zelené fluorescenční proteiny * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- luminescentní proteiny * MeSH
- zelené fluorescenční proteiny * MeSH