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Metastasis models for human tumors in athymic mice: useful models for drug development
D L Fine1, R Shoemaker, A Gazdar
1Program Resources, Inc., National Cancer Institute/Frederick Cancer Research Facility, MD 21701.
Abstract:
Although human tumor xenografts have been extensively used for preclinical evaluation of antitumor agents, most of this work has utilized subcutaneous or subrenal capsule assays based on change in tumor size. To obtain experimental models more reflective of the human clinical situations, we have developed several metastatic models that are based on and complement a panel of cell strains used in large-scale in vitro drug screening. One melanoma and four lung tumors produced metastatic lesions in the lung within 60 days following subcutaneous, intraperitoneal, or intrasplenic inoculation of BALB/C athymic nude mice. Several tumors also produced liver lesions, and one lung tumor strain showed metastasis to the brain. The metastatic lesions histologically resembled the tumors that grew at the inoculation site. In vitro and in vivo cell strains were rederived from the metastatic lesions. These systems may provide practical models for experimental drug and immunotherapeutic trials.
Insights
Researchers developed new metastatic cancer models in mice to better evaluate anti-cancer drugs. These models mimic human disease, offering improved preclinical testing for novel therapies and immunotherapies.
Area of Science:
- Oncology
- Preclinical Research
- Cancer Metastasis Models
Background:
- Traditional xenograft models often rely on tumor size, which may not accurately reflect clinical outcomes.
- Developing more clinically relevant preclinical models is crucial for effective anti-cancer drug evaluation.
Purpose of the Study:
- To establish and characterize novel metastatic cancer models in mice.
- To complement existing in vitro drug screening platforms with in vivo models that mimic human disease progression.
Main Methods:
- Developed several metastatic models using one melanoma and four lung tumor cell strains in BALB/C athymic nude mice.
- Utilized subcutaneous, intraperitoneal, and intrasplenic inoculation routes.
- Histologically analyzed metastatic lesions and rederived cell lines from these lesions for in vitro and in vivo studies.
Main Results:
- Metastatic lesions were observed in the lungs of mice within 60 days across multiple tumor types.
- Additional metastatic sites included the liver and, in one case, the brain.
- Histological similarity was confirmed between primary tumors and metastatic lesions.
- Viable cell lines were successfully rederived from metastatic sites.
Conclusions:
- The developed metastatic models provide a more clinically relevant platform for preclinical evaluation of anti-cancer agents.
- These models can be used in conjunction with in vitro drug screening.
- The models offer potential for experimental drug and immunotherapy trials, improving the translation of research findings to clinical practice.