Metastasis is a frequent cause of cancer-associated morbidity and mortality. Identification of genetic signatures or expression profiles which are associated with metastasis typically involves microarray analysis or genomic sequencing of isolated metastases, either in a clinical setting or animal models. In order to explore the contribution of individual genes to metastasis, we have developed an in vitro culture method for preferential expansion of breast cancer cells with high metastatic potential. Growing breast cancer cells in low growth factor, anchorage independent conditions maintains cells with low metastatic potential in a dormant or non-proliferative state while cells with more aggressive characteristics rapidly proliferate to form ascini. Low-throughput manual testing of this system is currently being carried out using two ‘dormant’ cell lines (PMC 42 LA and MCF-7) and one aggressive metastatic line (MDA MB 231) and ectopic expression of a subset of genes which we anticipate could promote metastasis (PTK2, MYLK, ROCK1, S100A4, Rad51 and ID1). In the high-content genetic screens, genes which cause a significant change in the number or size of ascini will be identified and validated in culture manually as well as in mouse models of breast cancer metastasis. The genetic data derived from these screens will identify genes which promote metastasis, yielding mechanistic information about the progress of metastatic disease. It will also provide convenient platform for testing therapeutic strategies to maintain micrometastases in a dormant state and prevent the onset of clinically relevant metastatic disease.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5138. doi:1538-7445.AM2012-5138