MCF-10A-NeoST: A new cell system for studying cell-ECM and cell-cell interactions in breast cancer

Purpose: There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. Experimental Design: We report here the isolation and initial characterizat ion of a spontaneously arising variant of MCF-10A. cells, NeoST, which prov ides a new model to study cell adhesion and signal transduction in breast c ancer. Results: NeoST cells recapitulate important biological and biochemical feat ures of metastatic breast cancer, including anchorage-independent growth, i nvasiveness in three-dimensional reconstituted membranes, loss of E-cadheri n expression, and increased tyrosine kinase activity. A comprehensive analy sis of tyrosine kinase expression revealed overexpression or functional act ivation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. Conclusions: MCF-10A and these new derivatives provide a genetically matche d model to study defects in cell adhesion and signaling that are relevant t o cellular behaviors that often typify aggressive breast cancer cells.