Regulation of Metastatic Breast Cancer Dormancy
Technical Report,01 Apr 2014,11 Sep 2015
University of Pittsburgh Pittsburgh United States
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Metastasis is a multistep process whereby cells from the primary tumor undergo an epithelial to mesenchymal transition EMT allowing for dissemination into metastatic niches such as the brain, bone and liver. Once attaining the metastatic organ the rate-limiting step in metastasis is that the cells must survive in a new niche and proliferate to form a frank metastasis. For reasons that are still incompletely understood, many breast cancer cells can remain dormant for years to even over a decade before proliferating into a distant macrometastasis. To begin to understand this important knowledge gap we have developed an all-human hepatic bioreactor. In this award period we have established that the hepatic bioreactor is functional for 30 days by functional and injury markers BUN, AST, ALT, CYP. We have generated micrometastases in the bioreactor and determined that breast cancer cell lines enter spontaneous dormancy in the bioreactor. We have also completed pilot experiments in mouse models for spontaneous metastasis formation with breast cancer cell lines.