期刊
ANTICANCER RESEARCH
卷 39, 期 5, 页码 2277-2287出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.13344
关键词
Mammary carcinoma; mammary epithelium; micro-environment; orthotopic tumor model; triple-negative breast cancer
类别
资金
- National Institute of General Medical Sciences, NIH [P20GM103499]
- USC School of Medicine Research and Development Fund
- MOHESR-Iraqi scholarship
- SPARC
- Canadian Institutes of Health [142353]
- USC Science Undergraduate Research Fellowship
- USC Magellan Scholar Award
- USC School of Medicine Research Program for Medical Students
- [R01CA218578]
- [P01AT003961-8455]
Background: Low success rates in oncology drug development are prompting re-evaluation of preclinical models, including orthotopic tumor engraftment. In breast cancer models, tumor cells are typically injected into mouse mammary fat pads (MFP). However, this approach bypasses the epithelial microenvironment, potentially altering tumor properties in ways that affect translational application. Materials and Methods: Tumors were generated by mammary intraductal (MIND) engraftment of 4T1 carcinoma cells. Growth, histopathology, and molecular features were quantified. Results: Despite growth similar to that of 4T1 MFP tumors, 4T1 MIND tumors exhibit distinct histopathology and increased metastasis. Furthermore, >6,000 transcripts were found to be uniquely up-regulated in 4T1 MIND tumor cells, including genes that drive several cancer hallmarks, in addition to two known therapeutic targets that were not up-regulated in 4T1 MFP tumor cells. Conclusion: Engraftment into the epithelial microenvironment generates tumors that more closely recapitulate the complexity of malignancy, suggesting that intraductal adaptation of orthotopic mammary models may be an important step towards improving outcomes in preclinical drug screening and development.
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