Summary of Invention
This invention is a panel of human breast cancer cell lines selected to metastasize to specific organs. The cell lines are useful both for studying the biological mechanisms of breast cancer metastasis and for screening compounds for anti-metastatic activity.
The SK1041 cell lines were derived from the human breast cancer cell line MDA-MB-231 following multiple rounds of in vivo selection in immunodeficient mice. They exhibit unique metastatic capacities compared to the parental MDA-MB-231 line, including organ-selective homing, distinct transcriptional profiles, and more aggressive phenotypes. The panel includes lung-, bone-, brain-, and adrenal-selective metastatic derivatives in addition to cell lines with increased capacity for tumor self-seeding, a process in which circulating tumor cells return to and grow in the primary tumor, promoting tumor progression and further metastasis. Subsets of these populations have been engineered to express reporter plasmids, including a novel triple-modality reporter that permits nuclear, fluorescent, and bioluminescence imaging in a single experimental model.
- Pure clonal populations of organ-tropic metastatic cells permit the selective study and comparison of biological mechanisms mediating metastasis to specific organs.
- In vivo metastatic lesions develop twice as fast and with a three-fold increase in penetrance compared to parental cell line (~6 weeks with ~90% penetrance vs. ~11 weeks with ~30% penetrance), reducing time and cost for each experiment.
- Aggressive phenotype allows facile detection of metastatic lesions by imaging and histochemical methods.
- These cell lines can be used for both in vivo and in vitro modeling (i.e. trans-well, Matrigel migration, etc.) of metastasis.
Areas of Application
- Research tool to study organ-tropic metastasis and tumor self-seeding
- Research tool for screening of potential anti-metastatic and anti-tumor self-seeding therapeutics
Stage of Development
Fully validated as an in vivo and in vitro research tool
Joan Massagué, PhD
Kannan Krishnamurthy, PhD