Abstract IA24: A stem cell program in early human metastatic breast cancer cells

In this study we used single-cell analysis to demonstrate that the initial disseminating metastatic cells resemble stem cells in their gene expression. We exploited patient-derived xenograft (PDX) models of human breast cancer to analyze metastatic cells in peripheral tissues. We developed a highly sensitive FACS-based assay to isolate and enumerate these metastatic cells. The primary tumor cells were heterogeneous and expressed high levels of luminal differentiation genes The metastatic cells from tissues with a low metastatic burden showed increased expression of stem cell, EMT, pro-survival, and dormancy-associated genes and differential expression of genes depending on the peripheral tissue. In contrast, in macrometastases, the cells were similar to primary tumor cells. The stem cell-like metastatic cells from low-burden tissues had significant tumor-initiating capacity upon transplantation, and differentiated to produce cancer cells with luminal gene expression. As the metastases progressed to a high metastatic burden the tumor cells showed increased expression of cMYC and proliferation-related genes. Our studies suggest that metastases are initiated by cells with stem cell character that upon proliferation and differentiation produce advanced metastatic disease and a poor outcome.References:Cheung, K.J., E. Gabrielson, Z. Werb & A. J. Ewald (2013). Collective invasion in breast cancer requires a conserved basal epithelial program. Cell. 155: 1639-1651.Plaks, V., N. ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Monitoring Metastasis and CTCs: Oral Presentations - Invited Abstracts Source Type: research