![]() We next demonstrated that this same basal molecular signature characterized the most invasive cells in 3D cultures of primary human breast tumors. ![]() K8+K14+ cancer cells led collective invasion and dissemination in 3D culture and in vivo in mouse models. We observed functional specialization of cancer cells into proliferative, non-invasive (K8+K14-) and non-proliferative, highly invasive (K8+K14+) phenotypes. ![]() cytokeratin-14+ (K14+)) across mouse models of three different molecular subtypes of breast cancer: luminal B, Her2+, and basal breast cancer. Collective invasion is led by cells with a basal molecular phenotype (e.g. The most important conclusion from our laboratory studies is that proliferation and invasion are driven by phenotypically distinct populations of cancer cells within the tumor. Tumor organoids are explanted into collagen I gels to model the collective invasion of breast tumors in the mammary stroma. Each organoid is composed of 200-500 epithelial cancer cells and reflects the cellular heterogeneity of the primary tumor. ![]() Briefly, we use enzymatic digestion to isolate thousands of “tumor organoids” from each primary tumor. Research in the Ewald laboratory starts from a simple question: which cells in a breast tumor are the most dangerous to the patient and most responsible for metastatic disease? To answer this question, we developed novel 3D culture assays to allow real-time analysis of invasion.
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